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1. Pharmacological activation of constitutive androstane receptor induces female-specific modulation of hepatic metabolism

Author

Huillet, Marine, Lasserre, Frédéric, Gratacap, Marie-Pierre, Engelmann, Beatrice, Bruse, Justine, Polizzi, Arnaud, Fougeray, Tiffany, Martin, Céline Marie Pauline, Rives, Clémence, Fougerat, Anne, Naylies, Claire, Lippi, Yannick, Garcia, Géraldine, Rousseau-Bacquie, Elodie, Canlet, Cécile, Debrauwer, Laurent, Rolle-Kampczyk, Ulrike, von Bergen, Martin, Payrastre, Bernard, Boutet-Robinet, Elisa, Gamet-Payrastre, Laurence, Guillou, Hervé, Loiseau, Nicolas, and Ellero-Simatos, Sandrine

Published
2024
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2. Measuring DNA modifications with the comet assay: a compendium of protocols

Author

Collins, Andrew, Møller, Peter, Gajski, Goran, Vodenková, Soňa, Abdulwahed, Abdulhadi, Anderson, Diana, Bankoglu, Ezgi Eyluel, Bonassi, Stefano, Boutet-Robinet, Elisa, Brunborg, Gunnar, Chao, Christy, Cooke, Marcus S., Costa, Carla, Costa, Solange, Dhawan, Alok, de Lapuente, Joaquin, Bo’, Cristian Del, Dubus, Julien, Dusinska, Maria, Duthie, Susan J., Yamani, Naouale El, Engelward, Bevin, Gaivão, Isabel, Giovannelli, Lisa, Godschalk, Roger, Guilherme, Sofia, Gutzkow, Kristine B., Habas, Khaled, Hernández, Alba, Herrero, Oscar, Isidori, Marina, Jha, Awadhesh N., Knasmüller, Siegfried, Kooter, Ingeborg M., Koppen, Gudrun, Kruszewski, Marcin, Ladeira, Carina, Laffon, Blanca, Larramendy, Marcelo, Hégarat, Ludovic Le, Lewies, Angélique, Lewinska, Anna, Liwszyc, Guillermo E., de Cerain, Adela López, Manjanatha, Mugimane, Marcos, Ricard, Milić, Mirta, de Andrade, Vanessa Moraes, Moretti, Massimo, Muruzabal, Damian, Novak, Matjaž, Oliveira, Rui, Olsen, Ann-Karin, Owiti, Norah, Pacheco, Mário, Pandey, Alok K., Pfuhler, Stefan, Pourrut, Bertrand, Reisinger, Kerstin, Rojas, Emilio, Rundén-Pran, Elise, Sanz-Serrano, Julen, Shaposhnikov, Sergey, Sipinen, Ville, Smeets, Karen, Stopper, Helga, Teixeira, João Paulo, Valdiglesias, Vanessa, Valverde, Mahara, van Acker, Frederique, van Schooten, Frederik-Jan, Vasquez, Marie, Wentzel, Johannes F., Wnuk, Maciej, Wouters, Annelies, Žegura, Bojana, Zikmund, Tomas, Langie, Sabine A. S., and Azqueta, Amaya

Published
2023
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3. 8-Alkynyl-3-nitroimidazopyridines display potent antitrypanosomal activity against both T. b. brucei and cruzi

Author

Fersing, Cyril, Boudot, Clotilde, Castera-Ducros, Caroline, Pinault, Emilie, Hutter, Sébastien, Paoli-Lombardo, Romain, Primas, Nicolas, Pedron, Julien, Seguy, Line, Bourgeade-Delmas, Sandra, Sournia-Saquet, Alix, Stigliani, Jean-Luc, Brossas, Jean-Yves, Paris, Luc, Valentin, Alexis, Wyllie, Susan, Fairlamb, Alan H., Boutet-Robinet, Élisa, Corvaisier, Sophie, Since, Marc, Malzert-Fréon, Aurélie, Destere, Alexandre, Mazier, Dominique, Rathelot, Pascal, Courtioux, Bertrand, Azas, Nadine, Verhaeghe, Pierre, and Vanelle, Patrice

Published
2020
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5. Minimum Information for Reporting on the Comet Assay (MIRCA): recommendations for describing comet assay procedures and results

Author

Møller, Peter, Azqueta, Amaya, Boutet-Robinet, Elisa, Koppen, Gudrun, Bonassi, Stefano, Milić, Mirta, Gajski, Goran, Costa, Solange, Teixeira, João Paulo, Costa Pereira, Cristiana, Dusinska, Maria, Godschalk, Roger, Brunborg, Gunnar, Gutzkow, Kristine B., Giovannelli, Lisa, Cooke, Marcus S., Richling, Elke, Laffon, Blanca, Valdiglesias, Vanessa, Basaran, Nursen, Del Bo’, Cristian, Zegura, Bojana, Novak, Matjaz, Stopper, Helga, Vodicka, Pavel, Vodenkova, Sona, de Andrade, Vanessa Moraes, Sramkova, Monika, Gabelova, Alena, Collins, Andrew, and Langie, Sabine A. S.

Published
2020
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6. Novel 8-nitroquinolin-2(1H)-ones as NTR-bioactivated antikinetoplastid molecules: Synthesis, electrochemical and SAR study

Author

Pedron, Julien, Boudot, Clotilde, Hutter, Sébastien, Bourgeade-Delmas, Sandra, Stigliani, Jean-Luc, Sournia-Saquet, Alix, Moreau, Alain, Boutet-Robinet, Elisa, Paloque, Lucie, Mothes, Emmanuelle, Laget, Michèle, Vendier, Laure, Pratviel, Geneviève, Wyllie, Susan, Fairlamb, Alan, Azas, Nadine, Courtioux, Bertrand, Valentin, Alexis, and Verhaeghe, Pierre

Published
2018
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10. Food-grade titanium dioxide translocates across the buccal mucosa in pigs and induces genotoxicity in an in vitro model of human oral epithelium

Author

Vignard, Julien, primary, Pettes-Duler, Aurelie, additional, Gaultier, Eric, additional, Cartier, Christel, additional, Weingarten, Laurent, additional, Biesemeier, Antje, additional, Taubitz, Tatjana, additional, Pinton, Philippe, additional, Bebeacua, Cecilia, additional, Devoille, Laurent, additional, Dupuy, Jacques, additional, Boutet-Robinet, Elisa, additional, Feltin, Nicolas, additional, Oswald, Isabelle P., additional, Pierre, Fabrice H., additional, Lamas, Bruno, additional, Mirey, Gladys, additional, and Houdeau, Eric, additional

Published
2023
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11. Measuring DNA modifications with the comet assay:a compendium of protocols

Author

Collins, Andrew, Moller, Peter, Gajski, Goran, Vodenkova, Sona, Abdulwahed, Abdulhadi, Anderson, Diana, Bankoglu, Ezgi Eyluel, Bonassi, Stefano, Boutet-Robinet, Elisa, Brunborg, Gunnar, Chao, Christy, Cooke, Marcus S. S., Costa, Carla, Costa, Solange, Dhawan, Alok, de Lapuente, Joaquin, Del Bo, Cristian, Dubus, Julien, Dusinska, Maria, Duthie, Susan J. J., El Yamani, Naouale, Engelward, Bevin, Gaivao, Isabel, Giovannelli, Lisa, Godschalk, Roger, Guilherme, Sofia, Gutzkow, Kristine B. B., Habas, Khaled, Hernandez, Alba, Herrero, Oscar, Isidori, Marina, Jha, Awadhesh N. N., Knasmueller, Siegfried, Kooter, Ingeborg M. M., Koppen, Gudrun, Kruszewski, Marcin, Ladeira, Carina, Laffon, Blanca, Larramendy, Marcelo, Le Hegarat, Ludovic, Lewies, Angelique, Lewinska, Anna, Liwszyc, Guillermo E. E., de Cerain, Adela Lopez, Manjanatha, Mugimane, Marcos, Ricard, Milic, Mirta, de Andrade, Vanessa Moraes, Moretti, Massimo, Muruzabal, Damian, Novak, Matjaz, Oliveira, Rui, Olsen, Ann-Karin, Owiti, Norah, Pacheco, Mario, Pandey, Alok K. K., Pfuhler, Stefan, Pourrut, Bertrand, Reisinger, Kerstin, Rojas, Emilio, Runden-Pran, Elise, Sanz-Serrano, Julen, Shaposhnikov, Sergey, Sipinen, Ville, Smeets, Karen, Stopper, Helga, Teixeira, Joao Paulo, Valdiglesias, Vanessa, Valverde, Mahara, van Acker, Frederique, van Schooten, Frederik-Jan, Vasquez, Marie, Wentzel, Johannes F. F., Wnuk, Maciej, Wouters, Annelies, Zegura, Bojana, Zikmund, Tomas, Langie, Sabine A. S., Azqueta, Amaya, Collins, Andrew, Moller, Peter, Gajski, Goran, Vodenkova, Sona, Abdulwahed, Abdulhadi, Anderson, Diana, Bankoglu, Ezgi Eyluel, Bonassi, Stefano, Boutet-Robinet, Elisa, Brunborg, Gunnar, Chao, Christy, Cooke, Marcus S. S., Costa, Carla, Costa, Solange, Dhawan, Alok, de Lapuente, Joaquin, Del Bo, Cristian, Dubus, Julien, Dusinska, Maria, Duthie, Susan J. J., El Yamani, Naouale, Engelward, Bevin, Gaivao, Isabel, Giovannelli, Lisa, Godschalk, Roger, Guilherme, Sofia, Gutzkow, Kristine B. B., Habas, Khaled, Hernandez, Alba, Herrero, Oscar, Isidori, Marina, Jha, Awadhesh N. N., Knasmueller, Siegfried, Kooter, Ingeborg M. M., Koppen, Gudrun, Kruszewski, Marcin, Ladeira, Carina, Laffon, Blanca, Larramendy, Marcelo, Le Hegarat, Ludovic, Lewies, Angelique, Lewinska, Anna, Liwszyc, Guillermo E. E., de Cerain, Adela Lopez, Manjanatha, Mugimane, Marcos, Ricard, Milic, Mirta, de Andrade, Vanessa Moraes, Moretti, Massimo, Muruzabal, Damian, Novak, Matjaz, Oliveira, Rui, Olsen, Ann-Karin, Owiti, Norah, Pacheco, Mario, Pandey, Alok K. K., Pfuhler, Stefan, Pourrut, Bertrand, Reisinger, Kerstin, Rojas, Emilio, Runden-Pran, Elise, Sanz-Serrano, Julen, Shaposhnikov, Sergey, Sipinen, Ville, Smeets, Karen, Stopper, Helga, Teixeira, Joao Paulo, Valdiglesias, Vanessa, Valverde, Mahara, van Acker, Frederique, van Schooten, Frederik-Jan, Vasquez, Marie, Wentzel, Johannes F. F., Wnuk, Maciej, Wouters, Annelies, Zegura, Bojana, Zikmund, Tomas, Langie, Sabine A. S., and Azqueta, Amaya

Abstract

The comet assay is a versatile method to detect nuclear DNA damage in individual eukaryotic cells, from yeast to human. The types of damage detected encompass DNA strand breaks and alkali-labile sites (e.g., apurinic/apyrimidinic sites), alkylated and oxidized nucleobases, DNA–DNA crosslinks, UV-induced cyclobutane pyrimidine dimers and some chemically induced DNA adducts. Depending on the specimen type, there are important modifications to the comet assay protocol to avoid the formation of additional DNA damage during the processing of samples and to ensure sufficient sensitivity to detect differences in damage levels between sample groups. Various applications of the comet assay have been validated by research groups in academia, industry and regulatory agencies, and its strengths are highlighted by the adoption of the comet assay as an in vivo test for genotoxicity in animal organs by the Organisation for Economic Co-operation and Development. The present document includes a series of consensus protocols that describe the application of the comet assay to a wide variety of cell types, species and types of DNA damage, thereby demonstrating its versatility., The comet assay is a versatile method to detect nuclear DNA damage in individual eukaryotic cells, from yeast to human. The types of damage detected encompass DNA strand breaks and alkali-labile sites (e.g., apurinic/apyrimidinic sites), alkylated and oxidized nucleobases, DNA-DNA crosslinks, UV-induced cyclobutane pyrimidine dimers and some chemically induced DNA adducts. Depending on the specimen type, there are important modifications to the comet assay protocol to avoid the formation of additional DNA damage during the processing of samples and to ensure sufficient sensitivity to detect differences in damage levels between sample groups. Various applications of the comet assay have been validated by research groups in academia, industry and regulatory agencies, and its strengths are highlighted by the adoption of the comet assay as an in vivo test for genotoxicity in animal organs by the Organisation for Economic Co-operation and Development. The present document includes a series of consensus protocols that describe the application of the comet assay to a wide variety of cell types, species and types of DNA damage, thereby demonstrating its versatility.The comet assay is commonly used to assess DNA damage. This collection of consensus protocols includes adaptations for a wide range of species and sample types, assay formats and detection of different types of DNA lesions.

Published
2023

12. Pharmacological activation of constitutive androstane receptor induces female-specific modulation of hepatic metabolism

Author

Huillet Marine, Lasserre Frédéric, Gratacap Marie-Pierre, Engelmann Beatrice, Bruse Justine, Polizzi Arnaud, Fougeray Tiffany, Martin Céline, Rives Clémence, Fougerat Anne, Naylies Claire, Lippi Yannick, Garcia Géraldine, Rousseau- Bacquie Elodie, Canlet Cécile, Debrauwer Laurent, Rolle-Kampczyk Ulrike, von Bergen Martin, Payrastre Bernard, Boutet-Robinet Elisa, Gamet-Payrastre Laurence, Guillou Hervé, Loiseau Nicolas, and Ellero-Simatos Sandrine

Abstract

Background and AimsThe constitutive androstane receptor (CAR) is a nuclear receptor able to recognize a large panel of xenobiotics leading to the modulation of the expression of its target genes involved in xenobiotic detoxication and energy metabolism. While CAR hepatic activity is thought to be higher in women than in men, its response to an acute pharmacological activation has never been investigated in both sexes.MethodsHepatic transcriptome, plasma and hepatic metabolome, have been analyzed inCar+/+andCar-/-male and female mice treated either with the CAR-specific agonist, 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), or with vehicle.ResultsWhile 90% of TCPOBOP-sensitive genes were modulated in a sex- independent way, the remaining 10% were almost exclusively impacted in female liver specifically. These female-specific CAR-sensitive genes were mainly involved in xenobiotic metabolism, inflammation and extracellular matrix organization. CAR activation also induced higher hepatic oxidative stress and hepatocyte cytolysis in females than in males. Data mining on human data confirmed that CAR activation may be involved in sexually-dimorphic drug-induced liver injury. Hepatic expression of flavin monooxygenase 3(Fmo3)was almost abolished and associated with a decrease of hepatic trimethylamine-N-oxide (TMAO) concentration in TCPOBOP-treated females. In line with a possible role in the control of TMAO homeostasis, CAR activation decreased platelet hyperresponsiveness in female mice supplemented with dietary choline.ConclusionsOur results demonstrate that more than 10% of CAR-sensitive genes are sex-specific and influence hepatic and systemic response such as platelet aggregation. Also, CAR activation may be an important mechanism of sexually- dimorphic drug-induced liver injury.

Published
2023

13. Haem iron reshapes colonic luminal environment: impact on mucosal homeostasis and microbiome through aldehyde formation

Author

Martin, Océane C. B., Olier, Maïwenn, Ellero-Simatos, Sandrine, Naud, Nathalie, Dupuy, Jacques, Huc, Laurence, Taché, Sylviane, Graillot, Vanessa, Levêque, Mathilde, Bézirard, Valérie, Héliès-Toussaint, Cécile, Estrada, Florence Blas Y., Tondereau, Valérie, Lippi, Yannick, Naylies, Claire, Peyriga, Lindsey, Canlet, Cécile, Davila, Anne Marie, Blachier, François, Ferrier, Laurent, Boutet-Robinet, Elisa, Guéraud, Françoise, Théodorou, Vassilia, and Pierre, Fabrice H. F.

Published
2019
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15. Human TR146 cells and pig buccal mucosa to assess oral transmucosal passage and buccal toxicity of foodgrade titanium dioxide

Author

Vignard, Julien, Pettes-Duler, Aurélie, Gaultier, Eric, Cartier, Christel, Weingarten, L., Biesemeier, A., Pinton, Philippe, Bebeacua, C., Devoille, Laurent, Dupuy, Jacques, Boutet-Robinet, Elisa, Feltin, Nicolas, Oswald, Isabelle P., Pierre, Fabrice H.F., Lamas, Bruno, Mirey, Gladys, Houdeau, Eric, Génotoxicité & Signalisation (ToxAlim-GS), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Endocrinologie & Toxicologie de la Barrière Intestinale (ToxAlim-ENTeRisk), Centre de microcaractérisation Raimond Castaing (Centre Castaing), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT), Luxembourg Institute of Science and Technology (LIST), Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Laboratoire National de Métrologie et d'Essais [Trappes] (LNE ), Prévention et promotion de la cancérogénèse par les aliments (ToxAlim-PPCA), and Toxicologie Intégrative & Métabolisme (ToxAlim-TIM)

Subjects
[SDV.TOX]Life Sciences [q-bio]/Toxicology, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; Background: Today, the use of titanium dioxide (TiO 2) as food additive (E171) has been banned by the European Commission, due to concerns for human health based on studies showing TiO 2 particles systematically available, tissue accumulation, a genotoxic risk and possible promotion of precancerous lesions. However, E171 is still present in toothpastes and pharmaceutical tablets as a whitening powder mixing nano-and submicronic particles. Risk assessment of TiO 2 intake by oral route is mainly based on the assumption that particles are mainly absorbed by the intestine. However, while the buccal mucosa is the first exposed area, the possibility of an oro-transmucosal passage has not been documented so far. In order to gain insight on possible adverse effects for human health associated to E171 buccal exposure, we analyzed in vivo the translocation of TiO 2 (E171) in the buccal mucosa of pigs used as human mouth model. Moreover, we evaluated in vitro the particle translocation on human buccal TR146 cell line, and measured cytotoxic and genotoxic effects on proliferative and differentiated epithelial cells. Methods & Results: Under realistic exposure conditions with 50 µg/ml of food-grade TiO 2 in water suspension (size distribution 20-440 nm; mean size of 105 nm) deposited under the tongue of pigs, TEM-EDX data revealed the presence of small aggregates of TiO 2 particles translocated into the buccal mucosa from 30 minutes of exposure, reaching submaxillary lymph nodes after 4 hours. In human TR146 cells exposed to E171, kinetic analysis using confocal, TEM and SIMS imaging showed progressive and large uptake of isolated or small aggregates of both submicronic and nanosized particles, showing high permeability capacity. At 2h of E171 exposure, cytotoxicity, genotoxicity and oxidative stress were investigated on both proliferative or differentiated TR146 cells, in comparison with two TiO 2 size standards of 115 nm and 21 nm in diameter. All tested TiO 2 particles were reported cytotoxic on proliferative TR146 cells, and this effect was almost abolished following differentiation. Oxidative stress and genotoxicity assessed through γH2AX and 53BP1 foci formation and comet assay were only reported for E171 sample and TiO 2 particles of 115 nm, suggesting the particles above 20 nm responsive of these effects, and mainly on proliferative cells. Conclusions: Taken together, these results show in vivo and in vitro that the buccal mucosa is an important absorption route for systemic passage of foodborne TiO 2 (E171) particles. In human cells, uptake of TiO2 particles was cytotoxic without size effects, while they generate further oxidative and genotoxic stresses in proliferative buccal cells, that could impair epithelium renewal in the mouth. Altogether, these data emphasize that buccal exposure should be considered for toxicokinetic and risk assessments of TiO2 in human when used as food additive, including in toothpaste and pharmaceutical formulations.

Published
2022

16. Food-grade titanium dioxide translocates across the oral mucosa in pigs and induces genotoxicity in an in vitro model of human oral epithelium

Author

Vignard, Julien, Pettes-Duler, Aurélie, Gaultier, Eric, Cartier, Christel, Weingarten, L., Biesemeier, A., Taubitz, T., Pinton, Philippe, Bebeacua, C., Devoille, Laurent, Dupuy, Jacques, Boutet-Robinet, Elisa, Feltin, Nicolas, Oswald, Isabelle P., Pierre, Fabrice H.F., Lamas, Bruno, Mirey, Gladys, Houdeau, Eric, Génotoxicité & Signalisation (ToxAlim-GS), ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT), Endocrinologie & Toxicologie de la Barrière Intestinale (ToxAlim-ENTeRisk), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de microcaractérisation Raimond Castaing (Centre Castaing), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT), Materials Research and Technology (MRT) Department, Luxembourg Institute of Science and Technology (LIST), Unité de recherche Pharmacologie-Toxicologie (UPT), Institut National de la Recherche Agronomique (INRA), Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), ETH Zurich, Scientific Center for Optical and Electron Microscopy, Laboratoire National de Métrologie et d'Essais [Trappes] (LNE ), Prévention et promotion de la cancérogénèse par les aliments (ToxAlim-PPCA), and Toxicologie Intégrative & Métabolisme (ToxAlim-TIM)

Subjects
food additive, titanium dioxide, [SDV.TOX]Life Sciences [q-bio]/Toxicology, genotoxicity, cytotoxicity, [SDV.IMM]Life Sciences [q-bio]/Immunology, nanoparticles, Oral mucosa, [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

Background Food-grade titanium dioxide (TiO2), composed of nano- and submicron-sized particles, is used worldwide in various foodstuffs, toothpastes and pharmaceutical tablets as a whitening and opacifying agent. Its use as a food additive (E171 in EU) has raised concerns for human health regarding its systemic availability, tissue accumulation, genotoxicity and promotion of precancerous lesions. However, although the buccal mucosa is the first area exposed, oral transmucosal passage of TiO2 particles has not been documented. Here we analyzed TiO2 (E171) particle translocation in vivo through the pig buccal mucosa and in vitro on human buccal TR146 cells, and the effects of E171 on proliferating and differentiated human oral epithelial cells. Results Using transmission electronic microscopy (TEM) coupled to energy-dispersive X-ray spectroscopy (EDX), isolated TiO2 particles and small aggregates were observed in the buccal floor of pigs starting 30 min after the sublingual deposition of E171 suspended in water, and recovered in the submandibular lymph nodes at 4 h. In human TR146 cells exposed to E171, kinetic analyses using confocal microscopy, TEM and high-resolution secondary ion mass spectrometry (SIMS) imaging showed high uptake capacities of both the nano- and submicron-sized TiO2 particles. At 2 h, the cytotoxicity, genotoxicity and oxidative stress were investigated in both proliferating and differentiated TR146 cells exposed to E171 in comparison with two TiO2 size standards of 115 and 21 nm in diameter. All TiO2 samples were reported cytotoxic in proliferating cells, an effect almost abolished following differentiation. Genotoxicity (γH2AX or 53BP1 foci formation and comet assays) and oxidative stress (CellRox reagent) were only reported for the E171 and 115 nm TiO2 particles, and mainly in proliferating cells. Conclusions These data showed that the buccal mucosa is an important absorption route for the systemic passage of food-grade TiO2 particles. In human cells, TiO2 particles are cytotoxic and generate size-dependent oxidative and genotoxic stresses in proliferating cells, potentially impairing oral epithelium renewal. Altogether, these data emphasize that buccal exposure should be considered during toxicokinetic studies and for risk assessment of TiO2 in human when used as food additive, including in toothpastes and pharmaceutical formulations.

Published
2022

18. Characterization of human isogenic epithelial cell lines as a relevant tool to study colon carcinogenesis and interaction between genes and environment

Author

Tête, Arnaud, Arnaud, Liana C., Le Mentec, Hélène, Gallais, Isabelle, Poupin, Nathalie, Tournadre, Noémie, Duarte-Hospital, Carolina, Lippi, Yannick, Mathevet, Fanny, Lefort, Gaëlle, Burel, Agnes, Surya, R., Boutet-Robinet, Elisa, Shay, Jerry W., Vialaneix, Nathalie, Bortoli, Sylvie, Lagadic-Gossmann, Dominique, Huc, Laurence, Vialaneix, Nathalie, Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Contaminants & Stress Cellulaire (ToxAlim-COMICS), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), EHESP-Irset (EHESP-Irset), École des Hautes Études en Santé Publique [EHESP] (EHESP), Métabolisme et Xénobiotiques (ToxAlim-MeX), Université Paris Descartes, Sorbonne Paris Cité, Transcriptomic impact of Xenobiotics (E23 TRiX), Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRAE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biosit : biologie, santé, innovation technologique (SFR UMS CNRS 3480 - INSERM 018), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Bina Nusantara University [Jakarta], University of Texas Southwestern Medical Center, and ITMO Cancer, METAhCOL

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, digestive system diseases
Abstract

International audience; Colorectal cancer (CRC) is the fourth most common cause of death from cancer worldwide. CRC is a multistep and progressive disease where genetic factors are important in the initiation, the development and the progression of the disease. CRC can arise from sequential steps including the acquisition of mutations in the adenomatous polyposis coli (APC), followed by the mutational activation of oncogene KRAS and the inactivation of the tumor suppressor gene, TP53. The occurrence of colorectal cancer is largely influenced by the environment, including food contaminants, lifestyle and nutrition. However, the influence of mutations on the response to environmental pollutants is poorly evaluated. Environmental carcinogenesis lacks robust models to explore the interaction between genes and environment and to determine whether genetic mutations associated with colon carcinogenesis generate a particular susceptibility to the harmful effects of pollutants. Here, we outline the characterization of an innovative cellular model that consists in 6 human isogenic epithelial colon cell lines bearing mutations on driver genes of CRC. Altogether, these cell lines recapitulate colon carcinogenesis from the healthy, preneoplastic, adenoma and carcinoma stages in a simplified way. We aim to perform a phenotypic and metabolic description of these cell lines, with a particular focus on their ability to express the battery of detoxification enzymes, to have a differential sensitivity to genotoxicity and cell death stimuli, to display a flexible energy metabolism, to migrate and grow without anchorage. We show that these models of human isogenic colonic cells of CRC could be a powerful and relevant tool to study the effects of environmental pollutants on the colorectal carcinogenesis from the early to the late and metastatic stages and to evaluate gene-environment interactions in food toxicology.

Published
2022

20. Longitudinal study of DNA in lymphocytes of female farmers measured using the alkaline comet assay and link with cancer development.

Author

Evenden, Poppy, primary, Lecluse, Yannick, additional, Lacauve, Anne-Sophie, additional, Niez, Elodie, additional, Perrier, Stéphanie, additional, Perdry, Hervé, additional, Boutet-Robinet, Elisa, additional, Morlais, Fabrice, additional, Tual, Séverine, additional, Boulanger, Mathilde, additional, Bonassi, Stefano, additional, Delépée, Raphaël, additional, Lebailly, Pierre, additional, and Meryet-Figuière, Matthieu, additional

Published
2022
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22. Characterization of human isogenic epithelial cell lines as a relevant tool to study colon carcinogenesis and interaction between genes and environment

Author

Tête, Arnaud, Arnaud, Liana C., Le Mentec, Hélène, Gallais, Isabelle, Tournadre, Noémie, Duarte-Hospital, Carolina, Lippi, Yannick, Mathevet, Fanny, Lefort, Gaëlle, Burel, Agnès, Surya, R., Boutet-Robinet, Elisa, Shay, Jerry W., Vialaneix, Nathalie, Bortoli, Sylvie, Lagadic-Gossmann, Dominique, Huc, Laurence, Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), EHESP-Irset (EHESP-Irset), École des Hautes Études en Santé Publique [EHESP] (EHESP), Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biosit : biologie, santé, innovation technologique (SFR UMS CNRS 3480 - INSERM 018), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Bina Nusantara University [Jakarta], University of Texas Southwestern Medical Center [Dallas], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRAE), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Vialaneix, Nathalie

Subjects
[STAT.AP]Statistics [stat]/Applications [stat.AP], [STAT.AP] Statistics [stat]/Applications [stat.AP], digestive system diseases
Abstract

International audience; Colorectal cancer (CRC) is the fourth most common cause of death from cancer worldwide. CRC is a multistep and progressive disease where genetic factors are important in the initiation, the development and the progression of the disease. Then, CRCs can arise from sequential steps including the acquisition of mutations in the adenomatous polyposis coli (APC), followed by the mutational activation of oncogene KRAS and the inactivation of the tumor suppressor gene, TP53. The occurrence of colorectal cancer is largely influenced by the environment, including food contaminants, lifestyle and nutrition. However, the influence of mutations on the response to environmental pollutants is poorly evaluated. Environmental carcinogenesis lacks robust models to explore the interaction between genes and environment and to determine whether genetic mutations associated with colon carcinogenesis generate a particular susceptibility to the harmful effects of pollutants.

Published
2021

23. O-123 DNA damage in lymphocytes of female farmers measured using the alkaline comet assay.

Author

Evenden, Poppy, primary, Lecluse, Yannick, additional, Lebailly, Pierre, additional, Perrier, Stephanie, additional, Boulanger, Mathilde, additional, Meryet-Figuière, Matthieu, additional, Lacauve, Anne-Sophie, additional, Niez, Elodie, additional, Perdry, Hervé, additional, Boutet-Robinet, Elisa, additional, Tual, Séverine, additional, Bonassi, Stefano, additional, and Delépée, Raphaël, additional

Published
2021
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24. Perception of pharmacy students toward opioid-related disorders and roles of community pharmacists: A French nationwide cross-sectional study

Author

Balayssac, David, primary, Pereira, Bruno, additional, Cuq, Pierre, additional, Douris, Juliette, additional, Ferrari, Luc, additional, Boutet-Robinet, Elisa, additional, Lechevrel, Mathilde, additional, Demeilliers, Christine, additional, Rat, Patrice, additional, Coudoré, François, additional, Verron, Elise, additional, Lacarelle, Bruno, additional, Guitton, Jérôme, additional, Courtois, Arnaud, additional, Allorge, Delphine, additional, Pain, Stéphanie, additional, Guerbet, Michel, additional, Collin, Aurore, additional, Vennat, Brigitte, additional, Brousse, Georges, additional, Authier, Nicolas, additional, and Laporte, Catherine, additional

Published
2021
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25. Short-Term and Long-Term Carcinogenic Effects of Food Contaminants (4-Hydroxynonenal and Pesticides) on Colorectal Human Cells: Involvement of Genotoxic and Non-Genomic Mechanisms

Author

Arnaud, Liana C., primary, Gauthier, Thierry, additional, Le Naour, Augustin, additional, Hashim, Saleha, additional, Naud, Nathalie, additional, Shay, Jerry W., additional, Pierre, Fabrice H., additional, Boutet-Robinet, Elisa, additional, and Huc, Laurence, additional

Published
2021
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26. Author Correction: DNA damage in circulating leukocytes measured with the comet assay may predict the risk of death (Scientific Reports, (2021), 11, 1, (16793), 10.1038/s41598-021-95976-7)

Author

Bonassi, Stefano, Ceppi,Marcello, Møller, Peter, Azqueta, Amaya, Milić, Mirta, Neri, Monica, Brunborg, Gunnar, Godschalk, Roger, Koppen, Gudrun, Langie, Sabine A. S., Teixeira, João Paulo, Bruzzone, Marco, Da Silva, Juliana, Benedetti, Danieli, Cavallo, Delia, Ursini, Cinzia Lucia, Giovannelli, Lisa, Moretti, Silvia, Riso, Patrizia, Del Bo’, Cristian, Russo, Patrizia, Dobrzyńska, Malgorzata, Goroshinskaya, Irina A., Surikova, Ekaterina I., Staruchova, Marta, Barančokova, Magdalena, Volkovova, Katarina, Kažimirova, Alena, Smolkova, Bozena, Laffon, Blanca, Valdiglesias, Vanessa, Pastor, Susana, Marcos, Ricard, Hernández, Alba, Gajski, Goran, Spremo-Potparević, Biljana, Živković, Lada, Boutet-Robinet, Elisa, Perdry, Hervé, Lebailly, Pierre, Perez, Carlos L., Basaran, Nursen, Nemeth, Zsuzsanna, Safar, Anna, Dusinska, Maria, Collins, Andrew, Anderson, Diana, Andrade, Vanessa, Pereira, Cristiana Costa, Costa, Solange, Gutzkow, Kristine B., Ladeira, Carina, Moretti, Massimo, Costa, Carla, Orlow, Irene, Rojas, Emilio, Pourrut, Bertrand, Kruszewski, Marcin, Knasmueller, Siegfried, Shaposhnikov, Sergey, Žegura, Bojana, and Stopper, Helga

Abstract

Link to the corrected article: [https://farfar.pharmacy.bg.ac.rs/handle/123456789/3944]

Published
2021

27. DNA damage in circulating leukocytes measured with the comet assay may predict the risk of death

Author

Bonassi, Stefano, Ceppi, Marcello, Møller, Peter, Azqueta, Amaya, Milić, Mirta, Monica, Neri, Brunborg, Gunnar, Godschalk, Roger, Koppen, Gudrun, Langie, Sabine A. S., Teixeira, João Paulo, Bruzzone, Marco, Da Silva, Juliana, Benedetti, Danieli, Cavallo, Delia, Ursini, Cinzia Lucia, Giovannelli, Lisa, Moretti, Silvia, Riso, Patrizia, Del Bo’, Cristian, Russo, Patrizia, Dobrzyńska, Malgorzata, Goroshinskaya, Irina A., Surikova, Ekaterina I., Staruchova, Marta, Barančokova, Magdalena, Volkovova, Katarina, Kažimirova, Alena, Smolkova, Bozena, Laffon, Blanca, Valdiglesias, Vanessa, Pastor, Susana, Marcos, Ricard, Hernández, Alba, Gajski, Goran, Spremo-Potparević, Biljana, Živković, Lada, Boutet-Robinet, Elisa, Perdry, Hervé, Lebailly, Pierre, Perez, Carlos L., Basaran, Nursen, Nemeth, Zsuzsanna, Safar, Anna, Dusinska, Maria, Collins, Andrew, Anderson, Diana, Andrade, Vanessa, Pereira, Cristiana Costa, Costa, Solange, Gutzkow, Kristine B., Ladeira, Carina, Moretti, Massimo, Costa, Carla, Orlow, Irene, Rojas, Emilio, Pourrut, Bertrand, Kruszewski, Marcin, Knasmueller, Siegfried, Shaposhnikov, Sergey, Žegura, Bojana, Stopper, Helga, LESUR, Hélène, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS San Raffaele Pisana), Ospedale Policlinico San Martino [Genoa], University of Copenhagen = Københavns Universitet (UCPH), Universidad de Navarra [Pamplona] (UNAV), Instituto de Investigación Sanitaria de Navarra [Pamplona, Spain] (IdiSNA), Institute for Medical Research and Occupational Health, Norwegian Institute of Public Health [Oslo] (NIPH), School of Nutrition and Translational Research in Metabolism [Maastricht] (NUTRIM), Maastricht University [Maastricht], Flemish Institute for Technological Research (VITO), Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), Universidade Luterana do Brasil - ULBRA (BRAZIL), Universidade Luterana do Brasil (ULBRA), Istituto Nazionale per l’Assicurazione contro gli Infortuni sul Lavoro [Italian Workers Compensation Authority] (INAIL), NEUROFARBA Department [Firenze, Italy], Università degli Studi di Firenze = University of Florence (UniFI), Université de Florence, Università degli Studi di Milano = University of Milan (UNIMI), IRCCS San Raffaele Scientific Institute [Milan, Italie], National Institute of Public Health - National Institute of Hygiene [Poland], N.N. Blokhin National Medical Research Center of Oncology, Slovak Medical University of Bratislava (SMU), Slovak Academy of Science [Bratislava] (SAS), University of A Coruña (UDC), Instituto de Investigación Biomédica de A Coruña [La Corogne, Espagne] (INIBIC), A Coruña University Hospital [La Corogne, Espagne], Universitat Autònoma de Barcelona (UAB), CIBER de Epidemiología y Salud Pública (CIBERESP), School of Medecine [Belgrade], University of Belgrade [Belgrade], Contaminants & Stress Cellulaire (ToxAlim-COMICS), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Instituto de Ciencias Básicas y Preclínicas Victoria de Girón, Hacettepe University = Hacettepe Üniversitesi, National center for public health [Hungary], Norwegian Institute for Air Research (NILU), University of Oslo (UiO), This article is based upon work from COST Action CA15132 (hCOMET), supported by COST (European Cooperation in Science and Technology). The work of SB and PR was supported by funds granted by the Italian Ministry of Health for Institutional Research (Ricerca Corrente)., Farmacologie en Toxicologie, RS: NUTRIM - R3 - Respiratory & Age-related Health, University of Copenhagen = Københavns Universitet (KU), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Università degli Studi di Milano [Milano] (UNIMI), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, and Instituto de Saúde Pública da Universidade do Porto

Subjects
Oncology, [SDV]Life Sciences [q-bio], Chromosomal aberrations, Human cancer, Lymphocytes, Predicts, Frequency, Validation, Biomarkers, Hallmarks, Adducts, Repair, Cohort, Kaplan-Meier Estimate, 0302 clinical medicine, Neoplasms, Leukocytes, Medicine, Gel electrophoresis, 0303 health sciences, Multidisciplinary, Hazard ratio, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Biomarker (medicine), LYMPHOCYTES PREDICTS, Comet Assay, Cell-Free Nucleic Acids, medicine.medical_specialty, DNA damage, Science, FREQUENCY, Article, VALIDATION, 03 medical and health sciences, ADDUCTS, Internal medicine, Humans, COHORT, Risk factor, Author Correction, 030304 developmental biology, Proportional Hazards Models, HALLMARKS, REPAIR, HUMAN CANCER, business.industry, Proportional hazards model, Comet assay, biomarker, leukocytes, epidemiology, Comet assay, CHROMOSOMAL-ABERRATIONS, Risk factors, Genotoxicidade Ambiental, business, DNA Damage
Abstract

Author Correction: https://doi.org/10.1038/s41598-021-98620-6. The original version of this Article contained errors: The spelling of the author Monica Neri was incorrectly given as Neri Monica; Additionally, Affiliation 39 was incorrectly given as ‘National Institute of Health, Lisbon, Portugal’, the correct affiliation is listed below: National Institute of Health Doutor Ricardo Jorge, Porto, Portugal. The original Article has been corrected. [Abstract] The comet assay or single cell gel electrophoresis, is the most common method used to measure strand breaks and a variety of other DNA lesions in human populations. To estimate the risk of overall mortality, mortality by cause, and cancer incidence associated to DNA damage, a cohort of 2,403 healthy individuals (25,978 person-years) screened in 16 laboratories using the comet assay between 1996 and 2016 was followed-up. Kaplan–Meier analysis indicated a worse overall survival in the medium and high tertile of DNA damage (p

Published
2021

28. The hCOMET project: International database comparison of results with the comet assay in human biomonitoring. Baseline frequency of DNA damage and effect of main confounders

Author

Milić, Mirta, Ceppi, Marcello, Bruzzone, Marco, Azqueta, Amaya, Brunborg, Gunnar, Godschalk, Roger, Koppen, Gudrun, Langie, Sabine, Møller, Peter, Teixeira, João Paulo, Alija, Avdulla, Anderson, Diana, Andrade, Vanessa, Andreoli, Cristina, Asllani, Fisnik, Bangkoglu, Ezgi Eyluel, Barančoková, Magdalena, Basaran, Nursen, Boutet-Robinet, Elisa, Buschini, Annamaria, Cavallo, Delia, Costa Pereira, Cristiana, Costa, Carla, Costa, Solange, Da Silva, Juliana, Del Boˊ, Cristian, Dimitrijević Srećković, Vesna, Đelić, Ninoslav, Dobrzyńska, Malgorzata, Duračková, Zdenka, Dvořáková, Monika, Gajski, Goran, Galati, Serena, García Lima, Omar, Giovannelli, Lisa, Goroshinskaya, Irina A., Grindel, Annemarie, Gutzkow, Kristine B., Hernández, Alba, Hernández, Carlos, Holven, Kirsten B., Ibero-Baraibar, Idoia, Ottestad, Inger, Kadioglu, Ela, Kažimirová, Alena, Kuznetsova, Elena, Ladeira, Carina, Laffon, Blanca, Lamonaca, Palma, Lebailly, Pierre, Louro, Henriqueta, Mandina Cardoso, Tania, Marcon, Francesca, Marcos, Ricard, Moretti, Massimo, Moretti, Silvia, Najafzadeh, Mojgan, Nemeth, Zsuzsanna, Neri, Monica, Novotna, Bozena, Orlow, Irene, Paduchova, Zuzana, Pastor, Susana, Perdry, Hervé, Spremo-Potparević, Biljana, Ramadhani, Dwi, Riso, Patrizia, Rohr, Paula, Rojas, Emilio, Rossner, Pavel, Safar, Anna, Sardas, Semra, Silva, Maria João, Sirota, Nikolay, Smolkova, Bozena, Staruchova, Marta, Stetina, Rudolf, Stopper, Helga, Surikova, Ekaterina I., Ulven, Stine M., Ursini, Cinzia Lucia, Valdiglesias, Vanessa, Valverde, Mahara, Vodicka, Pavel, Volkovova, Katarina, Wagner, Karl-Heinz, Živković, Lada, Dušinská, Maria, Collins, Andrew R., Bonassi, Stefano, Milić, Mirta, Ceppi, Marcello, Bruzzone, Marco, Azqueta, Amaya, Brunborg, Gunnar, Godschalk, Roger, Koppen, Gudrun, Langie, Sabine, Møller, Peter, Teixeira, João Paulo, Alija, Avdulla, Anderson, Diana, Andrade, Vanessa, Andreoli, Cristina, Asllani, Fisnik, Bangkoglu, Ezgi Eyluel, Barančoková, Magdalena, Basaran, Nursen, Boutet-Robinet, Elisa, Buschini, Annamaria, Cavallo, Delia, Costa Pereira, Cristiana, Costa, Carla, Costa, Solange, Da Silva, Juliana, Del Boˊ, Cristian, Dimitrijević Srećković, Vesna, Đelić, Ninoslav, Dobrzyńska, Malgorzata, Duračková, Zdenka, Dvořáková, Monika, Gajski, Goran, Galati, Serena, García Lima, Omar, Giovannelli, Lisa, Goroshinskaya, Irina A., Grindel, Annemarie, Gutzkow, Kristine B., Hernández, Alba, Hernández, Carlos, Holven, Kirsten B., Ibero-Baraibar, Idoia, Ottestad, Inger, Kadioglu, Ela, Kažimirová, Alena, Kuznetsova, Elena, Ladeira, Carina, Laffon, Blanca, Lamonaca, Palma, Lebailly, Pierre, Louro, Henriqueta, Mandina Cardoso, Tania, Marcon, Francesca, Marcos, Ricard, Moretti, Massimo, Moretti, Silvia, Najafzadeh, Mojgan, Nemeth, Zsuzsanna, Neri, Monica, Novotna, Bozena, Orlow, Irene, Paduchova, Zuzana, Pastor, Susana, Perdry, Hervé, Spremo-Potparević, Biljana, Ramadhani, Dwi, Riso, Patrizia, Rohr, Paula, Rojas, Emilio, Rossner, Pavel, Safar, Anna, Sardas, Semra, Silva, Maria João, Sirota, Nikolay, Smolkova, Bozena, Staruchova, Marta, Stetina, Rudolf, Stopper, Helga, Surikova, Ekaterina I., Ulven, Stine M., Ursini, Cinzia Lucia, Valdiglesias, Vanessa, Valverde, Mahara, Vodicka, Pavel, Volkovova, Katarina, Wagner, Karl-Heinz, Živković, Lada, Dušinská, Maria, Collins, Andrew R., and Bonassi, Stefano

Abstract

The alkaline comet assay, or single cell gel electrophoresis, is one of the most popular methods for assessing DNA damage in human population. One of the open issues concerning this assay is the identification of those factors that can explain the large inter-individual and inter-laboratory variation. International collaborative initiatives such as the hCOMET project - a COST Action launched in 2016 - represent a valuable tool to meet this challenge. The aims of hCOMET were to establish reference values for the level of DNA damage in humans, to investigate the effect of host factors, lifestyle and exposure to genotoxic agents, and to compare different sources of assay variability. A database of 19,320 subjects was generated, pooling data from 105 studies run by 44 laboratories in 26 countries between 1999 and 2019. A mixed random effect log-linear model, in parallel with a classic meta-analysis, was applied to take into account the extensive heterogeneity of data, due to descriptor, specimen and protocol variability. As a result of this analysis interquartile intervals of DNA strand breaks (which includes alkali-labile sites) were reported for tail intensity, tail length, and tail moment (comet assay descriptors). A small variation by age was reported in some datasets, suggesting higher DNA damage in oldest age-classes, while no effect could be shown for sex or smoking habit, although the lack of data on heavy smokers has still to be considered. Finally, highly significant differences in DNA damage were found for most exposures investigated in specific studies. In conclusion, these data, which confirm that DNA damage measured by the comet assay is an excellent biomarker of exposure in several conditions, may contribute to improving the quality of study design and to the standardization of results of the comet assay in human populations.

Published
2021

29. Influence of the microenvironment on modulation of the host response by typhoid toxin

Author

Martin, Océane C.B., Bergonzini, Anna, Lopez Chiloeches, Maria, Paparouna, Eleni, Butter, Deborah, Theodorou, Sofia D.P., Haykal, Maria M., Boutet-Robinet, Elisa, Tebaldi, Toma, Wakeham, Andrew, Rhen, Mikael, Gorgoulis, Vassilis G., Mak, Tak, Pateras, Ioannis S., Frisan, Teresa, Martin, Océane C.B., Bergonzini, Anna, Lopez Chiloeches, Maria, Paparouna, Eleni, Butter, Deborah, Theodorou, Sofia D.P., Haykal, Maria M., Boutet-Robinet, Elisa, Tebaldi, Toma, Wakeham, Andrew, Rhen, Mikael, Gorgoulis, Vassilis G., Mak, Tak, Pateras, Ioannis S., and Frisan, Teresa

Abstract

Bacterial genotoxins cause DNA damage in eukaryotic cells, resulting in activation of the DNA damage response (DDR) in vitro. These toxins are produced by Gram-negative bacteria, enriched in the microbiota of inflammatory bowel disease (IBD) and colorectal cancer (CRC) patients. However, their role in infection remains poorly characterized. We address the role of typhoid toxin in modulation of the host-microbial interaction in health and disease. Infection with a genotoxigenic Salmonella protects mice from intestinal inflammation. We show that the presence of an active genotoxin promotes DNA fragmentation and senescence in vivo, which is uncoupled from an inflammatory response and unexpectedly associated with induction of an anti-inflammatory environment. The anti-inflammatory response is lost when infection occurs in mice with acute colitis. These data highlight a complex context-dependent crosstalk between bacterial-genotoxin-induced DDR and the host immune response, underlining an unexpected role for bacterial genotoxins.

Published
2021
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30. Detection of DNA damage by alkaline comet assay in mouse colonic mucosa

Author

Boutet-Robinet, Elisa, Haykal, Maria M., Hashim, Saleha, Frisan, Teresa, Martin, Océane C.B., Boutet-Robinet, Elisa, Haykal, Maria M., Hashim, Saleha, Frisan, Teresa, and Martin, Océane C.B.

Abstract

We recently characterized the association between DNA damage and immunoresponse in vivo in colonic mucosa of mice infected with a Salmonella Typhimurium strain expressing a genotoxin, known as typhoid toxin. In this protocol, we describe the specific steps for assessing DNA damage by the alkaline comet assay of colonic mucosal samples. The description of the comet assay protocol follows the international guidelines (Minimum Information for Reporting on the Comet Assay [Moller et al., 2020]). For complete details on the use and execution of this protocol, please refer to Martin et al. (2021).

Published
2021
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31. Collection and storage of human white blood cells for analysis of DNA damage and repair activity using the comet assay in molecular epidemiology studies

Author

Møller, Peter, Bankoglu, Ezgi Eyluel, Stopper, Helga, Giovannelli, Lisa, Ladeira, Carina, Koppen, Gudrun, Gajski, Goran, Collins, Andrew, Valdiglesias, Vanessa, Laffon, Blanca, Boutet-Robinet, Elisa, Perdry, Herve, Del Bo', Cristian, Langie, Sabine A. S., Dusinska, Maria, Azqueta, Amaya, Møller, Peter, Bankoglu, Ezgi Eyluel, Stopper, Helga, Giovannelli, Lisa, Ladeira, Carina, Koppen, Gudrun, Gajski, Goran, Collins, Andrew, Valdiglesias, Vanessa, Laffon, Blanca, Boutet-Robinet, Elisa, Perdry, Herve, Del Bo', Cristian, Langie, Sabine A. S., Dusinska, Maria, and Azqueta, Amaya

Abstract

DNA damage and repair activity are often assessed in blood samples from humans in different types of molecular epidemiology studies. However, it is not always feasible to analyse the samples on the day of collection without any type of storage. For instance, certain studies use repeated sampling of cells from the same subject or samples from different subjects collected at different time-points, and it is desirable to analyse all these samples in the same comet assay experiment. In addition, flawless comet assay analyses on frozen samples open up the possibility of using this technique on biobank material. In this article we discuss the use of cryopreserved peripheral blood mononuclear cells (PBMCs), buffy coat (BC) and whole blood (WB) for analysis of DNA damage and repair using the comet assay. The published literature and the authors' experiences indicate that various types of blood samples can be cryopreserved with only a minor effect on the basal level of DNA damage. There is evidence to suggest that WB and PBMCs can be cryopreserved for several years without much effect on the level of DNA damage. However, care should be taken when cryopreserving WB and BCs. It is possible to use either fresh or frozen samples of blood cells, but results from fresh and frozen cells should not be used in the same dataset. The article outlines detailed protocols for the cryopreservation of PBMCs, BCs and WB samples.

Published
2021

32. The hCOMET project:International database comparison of results with the comet assay in human biomonitoring. Baseline frequency of DNA damage and effect of main confounders

Author

Mili, Mirta, Ceppi, Marcello, Bruzzone, Marco, Azqueta, Amaya, Brunborg, Gunnar, Godschalk, Roger, Koppen, Gudrun, Langie, Sabine, Møller, Peter, Teixeira, Joao Paulo, Alija, Avdulla, Anderson, Diana, Andrade, Vanessa, Andreoli, Cristina, Asllani, Fisnik, Bangkoglu, Ezgi Eyluel, Barancokova, Magdalena, Basaran, Nursen, Boutet-Robinet, Elisa, Buschini, Annamaria, Cavallo, Delia, Pereira, Cristiana Costa, Costa, Carla, Costa, Solange, Silva, Juliana Da, Bo, Cristian Del, Sreckovic, Vesna Dimitrijevic, Djelic, Ninoslav, Durackova, Zdenka, Dvorakova, Monika, Gajski, Goran, Galati, Serena, Lima, Omar Garcia, Giovannelli, Lisa, Goroshinskaya, Irina A., Grindel, Annemarie, Gutzkow, Kristine B., Hernandez, Alba, Hernandez, Carlos, Holven, Kirsten B., Ibero-Baraibar, Idoia, Ottestad, Inger, Kadioglu, Ela, Kazimirova, Alena, Kuznetsova, Elena, Ladeira, Carina, Laffon, Blanca, Lamonaca, Palma, Lebailly, Pierre, Louro, Henriqueta, Cardoso, Tania Mandina, Marcon, Francesca, Marcos, Ricard, Moretti, Massimo, Moretti, Silvia, Najafzadeh, Mojgan, Nemeth, Zsuzsanna, Neri, Monica, Novotna, Bozena, Orlow, Irene, Paduchova, Zuzana, Pastor, Susana, Perdry, Herve, Spremo-Potparevic, Biljana, Ramadhani, Dwi, Riso, Patrizia, Rohr, Paula, Rojas, Emilio, Rossner, Pavel, Safar, Anna, Sardas, Semra, Silva, Maria Joao, Sirota, Nikolay, Smolkova, Bozena, Staruchova, Marta, Stetina, Rudolf, Stopper, Helga, Surikova, Ekaterina I., Ulven, Stine M., Ursini, Cinzia Lucia, Valdiglesias, Vanessa, Valverde, Mahara, Vodicka, Pavel, Volkovova, Katarina, Wagner, Karl-Heinz, Zivkovic, Lada, Dusinska, Maria, Collins, Andrew R., Bonassi, Stefano, Mili, Mirta, Ceppi, Marcello, Bruzzone, Marco, Azqueta, Amaya, Brunborg, Gunnar, Godschalk, Roger, Koppen, Gudrun, Langie, Sabine, Møller, Peter, Teixeira, Joao Paulo, Alija, Avdulla, Anderson, Diana, Andrade, Vanessa, Andreoli, Cristina, Asllani, Fisnik, Bangkoglu, Ezgi Eyluel, Barancokova, Magdalena, Basaran, Nursen, Boutet-Robinet, Elisa, Buschini, Annamaria, Cavallo, Delia, Pereira, Cristiana Costa, Costa, Carla, Costa, Solange, Silva, Juliana Da, Bo, Cristian Del, Sreckovic, Vesna Dimitrijevic, Djelic, Ninoslav, Durackova, Zdenka, Dvorakova, Monika, Gajski, Goran, Galati, Serena, Lima, Omar Garcia, Giovannelli, Lisa, Goroshinskaya, Irina A., Grindel, Annemarie, Gutzkow, Kristine B., Hernandez, Alba, Hernandez, Carlos, Holven, Kirsten B., Ibero-Baraibar, Idoia, Ottestad, Inger, Kadioglu, Ela, Kazimirova, Alena, Kuznetsova, Elena, Ladeira, Carina, Laffon, Blanca, Lamonaca, Palma, Lebailly, Pierre, Louro, Henriqueta, Cardoso, Tania Mandina, Marcon, Francesca, Marcos, Ricard, Moretti, Massimo, Moretti, Silvia, Najafzadeh, Mojgan, Nemeth, Zsuzsanna, Neri, Monica, Novotna, Bozena, Orlow, Irene, Paduchova, Zuzana, Pastor, Susana, Perdry, Herve, Spremo-Potparevic, Biljana, Ramadhani, Dwi, Riso, Patrizia, Rohr, Paula, Rojas, Emilio, Rossner, Pavel, Safar, Anna, Sardas, Semra, Silva, Maria Joao, Sirota, Nikolay, Smolkova, Bozena, Staruchova, Marta, Stetina, Rudolf, Stopper, Helga, Surikova, Ekaterina I., Ulven, Stine M., Ursini, Cinzia Lucia, Valdiglesias, Vanessa, Valverde, Mahara, Vodicka, Pavel, Volkovova, Katarina, Wagner, Karl-Heinz, Zivkovic, Lada, Dusinska, Maria, Collins, Andrew R., and Bonassi, Stefano

Abstract

The alkaline comet assay, or single cell gel electrophoresis, is one of the most popular methods for assessing DNA damage in human population. One of the open issues concerning this assay is the identification of those factors that can explain the large inter-individual and inter-laboratory variation. International collaborative initiatives such as the hCOMET project a COST Action launched in 2016 represent a valuable tool to meet this challenge. The aims of hCOMET were to establish reference values for the level of DNA damage in humans, to investigate the effect of host factors, lifestyle and exposure to genotoxic agents, and to compare different sources of assay variability. A database of 19,320 subjects was generated, pooling data from 105 studies run by 44 laboratories in 26 countries between 1999 and 2019. A mixed random effect log-linear model, in parallel with a classic meta-analysis, was applied to take into account the extensive heterogeneity of data, due to descriptor, specimen and protocol variability. As a result of this analysis interquartile intervals of DNA strand breaks (which includes alkali-labile sites) were reported for tail intensity, tail length, and tail moment (comet assay descriptors). A small variation by age was reported in some datasets, suggesting higher DNA damage in oldest age-classes, while no effect could be shown for sex or smoking habit, although the lack of data on heavy smokers has still to be considered. Finally, highly significant differences in DNA damage were found for most exposures investigated in specific studies. In conclusion, these data, which confirm that DNA damage measured by the comet assay is an excellent biomarker of exposure in several conditions, may contribute to improving the quality of study design and to the standardization of results of the comet assay in human populations.(c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creative

Published
2021

34. Influence of the microenvironment on modulation of the host response by typhoid toxin

Author

Martin, Océane C.B., primary, Bergonzini, Anna, additional, Lopez Chiloeches, Maria, additional, Paparouna, Eleni, additional, Butter, Deborah, additional, Theodorou, Sofia D.P., additional, Haykal, Maria M., additional, Boutet-Robinet, Elisa, additional, Tebaldi, Toma, additional, Wakeham, Andrew, additional, Rhen, Mikael, additional, Gorgoulis, Vassilis G., additional, Mak, Tak, additional, Pateras, Ioannis S., additional, and Frisan, Teresa, additional

Published
2021
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35. Collection and storage of human white blood cells for analysis of DNA damage and repair activity using the comet assay in molecular epidemiology studies

Author

Møller, Peter, primary, Bankoglu, Ezgi Eyluel, additional, Stopper, Helga, additional, Giovannelli, Lisa, additional, Ladeira, Carina, additional, Koppen, Gudrun, additional, Gajski, Goran, additional, Collins, Andrew, additional, Valdiglesias, Vanessa, additional, Laffon, Blanca, additional, Boutet-Robinet, Elisa, additional, Perdry, Hervé, additional, Del Bo’, Cristian, additional, Langie, Sabine A S, additional, Dusinska, Maria, additional, and Azqueta, Amaya, additional

Published
2021
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37. New 8-Nitroquinolinone Derivative Displaying Submicromolar in Vitro Activities against Both Trypanosoma brucei and cruzi

Author

Pedron, Julien, Boudot, Clotilde, Brossas, Jean-Yves, Pinault, Emilie, Bourgeade-Delmas, Sandra, Sournia-Saquet, Alix, Boutet-Robinet, Elisa, Destere, Alexandre, Tronnet, Antoine, Bergé, Justine, Bonduelle, Colin, Deraeve, Céline, Pratviel, Geneviève, Stigliani, Jean-Luc, Paris, Luc, Mazier, Dominique, Corvaisier, Sophie, Since, Marc, Malzert-Fréon, Aurélie, Malzert-Freón, Aureĺie, Wyllie, Susan, Milne, Rachel, Fairlamb, Alan, Valentin, Alexis, Courtioux, Bertrand, Verhaeghe, Pierre, Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Université de Limoges (UNILIM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT), Contaminants & Stress Cellulaire (ToxAlim-COMICS), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Pharmacologie, toxicologie et pharmacovigilance [CHU Limoges], CHU Limoges, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), University of Dundee, Paul Sabatier University, Région Occitanie, Wellcome Trust (WT105021), Institut Pasteur de Lille, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d'Immunologie et de Maladies Infectieuses (CIMI), LCC-CNRS, Université de Toulouse, CNRS, UPS, Toulouse, France, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Laboratoire Hétérochimie Fondamentale et Appliquée (LHFA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Immunité et Infection, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR113-Université Pierre et Marie Curie - Paris 6 (UPMC), Department of Biochemistry, Medical Sciences Institute, Dundee University, Dundee, Grelier, Elisabeth, Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], and Université Fédérale Toulouse Midi-Pyrénées

Subjects
Letter, Trypanosoma cruzi, Trypanosoma brucei brucei, Trypanosoma brucei, 01 natural sciences, Biochemistry, Drug Discovery, parasitic diseases, NTR1, [CHIM.COOR]Chemical Sciences/Coordination chemistry, redox potentials, biology, 010405 organic chemistry, Chemistry, 8-nitroquinolin-2(1H)-ones, Organic Chemistry, [CHIM.COOR] Chemical Sciences/Coordination chemistry, biology.organism_classification, In vitro, 0104 chemical sciences, 3. Good health, 010404 medicinal & biomolecular chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Pharmacophore
Abstract

International audience; An antikinetoplastid pharmacomodulation study was conducted at position 6 of the 8-nitroquinolin-2(1H)-one pharmacophore. Fifteen new derivatives were synthesized and evaluated in vitro against L. infantum, T. brucei brucei, and T. cruzi, in parallel with a cytotoxicity assay on the human HepG2 cell line. A potent and selective 6-bromo-substituted antitrypanosomal derivative 12 was revealed, presenting EC50 values of 12 and 500 nM on T. b. brucei trypomastigotes and T. cruzi amastigotes respectively, in comparison with four reference drugs (30 nM ≤ EC50 ≤ 13 μM). Moreover, compound 12 was not genotoxic in the comet assay and showed high in vitro microsomal stability (half life >40 min) as well as favorable pharmacokinetic behavior in the mouse after oral administration. Finally, molecule 12 (E° = −0.37 V/NHE) was shown to be bioactivated by type 1 nitroreductases, in both Leishmania and Trypanosoma, and appears to be a good candidate to search for novel antitrypanosomal lead compounds.

Published
2020

38. Minimum Information for Reporting on the Comet Assay (MIRCA):recommendations for describing comet assay procedures and results

Author

Møller, Peter, Azqueta, Amaya, Boutet-Robinet, Elisa, Koppen, Gudrun, Bonassi, Stefano, Milić, Mirta, Gajski, Goran, Costa, Solange, Teixeira, João Paulo, Costa Pereira, Cristiana, Dusinska, Maria, Godschalk, Roger, Brunborg, Gunnar, Gutzkow, Kristine B., Giovannelli, Lisa, Cooke, Marcus S., Richling, Elke, Laffon, Blanca, Valdiglesias, Vanessa, Basaran, Nursen, Del Bo’, Cristian, Zegura, Bojana, Novak, Matjaz, Stopper, Helga, Vodicka, Pavel, Vodenkova, Sona, de Andrade, Vanessa Moraes, Sramkova, Monika, Gabelova, Alena, Collins, Andrew, Langie, Sabine A.S., Møller, Peter, Azqueta, Amaya, Boutet-Robinet, Elisa, Koppen, Gudrun, Bonassi, Stefano, Milić, Mirta, Gajski, Goran, Costa, Solange, Teixeira, João Paulo, Costa Pereira, Cristiana, Dusinska, Maria, Godschalk, Roger, Brunborg, Gunnar, Gutzkow, Kristine B., Giovannelli, Lisa, Cooke, Marcus S., Richling, Elke, Laffon, Blanca, Valdiglesias, Vanessa, Basaran, Nursen, Del Bo’, Cristian, Zegura, Bojana, Novak, Matjaz, Stopper, Helga, Vodicka, Pavel, Vodenkova, Sona, de Andrade, Vanessa Moraes, Sramkova, Monika, Gabelova, Alena, Collins, Andrew, and Langie, Sabine A.S.

Abstract

The comet assay is a widely used test for the detection of DNA damage and repair activity. However, there are interlaboratory differences in reported levels of baseline and induced damage in the same experimental systems. These differences may be attributed to protocol differences, although it is difficult to identify the relevant conditions because detailed comet assay procedures are not always published. Here, we present a Consensus Statement for the Minimum Information for Reporting Comet Assay (MIRCA) providing recommendations for describing comet assay conditions and results. These recommendations differentiate between ‘desirable’ and ‘essential’ information: ‘essential’ information refers to the precise details that are necessary to assess the quality of the experimental work, whereas ‘desirable’ information relates to technical issues that might be encountered when repeating the experiments. Adherence to MIRCA recommendations should ensure that comet assay results can be easily interpreted and independently verified by other researchers.

Published
2020

39. Application of the comet assay in human biomonitoring:An hCOMET perspective

Author

Azqueta, Amaya, Ladeira, Carina, Giovannelli, Lisa, Boutet-Robinet, Elisa, Bonassi, Stefano, Neri, Monica, Gajski, Goran, Duthie, Susan, Del Bo’, Cristian, Riso, Patrizia, Koppen, Gudrun, Basaran, Nursen, Collins, Andrew, Møller, Peter, Azqueta, Amaya, Ladeira, Carina, Giovannelli, Lisa, Boutet-Robinet, Elisa, Bonassi, Stefano, Neri, Monica, Gajski, Goran, Duthie, Susan, Del Bo’, Cristian, Riso, Patrizia, Koppen, Gudrun, Basaran, Nursen, Collins, Andrew, and Møller, Peter

Abstract

The comet assay is a well-accepted biomonitoring tool to examine the effect of dietary, lifestyle, environmental and occupational exposure on levels of DNA damage in human cells. With such a wide range of determinants for DNA damage levels, it becomes challenging to deal with confounding and certain factors are inter-related (e.g. poor nutritional intake may correlate with smoking status). This review describes the effect of intrinsic (i.e. sex, age, tobacco smoking, occupational exposure and obesity) and extrinsic (season, environmental exposures, diet, physical activity and alcohol consumption) factors on the level of DNA damage measured by the standard or enzyme-modified comet assay. Although each factor influences at least one comet assay endpoint, the collective evidence does not indicate single factors have a large impact. Thus, controlling for confounding may be necessary in a biomonitoring study, but none of the factors is strong enough to be regarded a priori as a confounder. Controlling for confounding in the comet assay requires a case-by-case approach. Inter-laboratory variation in levels of DNA damage and to some extent also reproducibility in biomonitoring studies are issues that have haunted the users of the comet assay for years. Procedures to collect specimens, and their storage, are not standardized. Likewise, statistical issues related to both sample-size calculation (before sampling of specimens) and statistical analysis of the results vary between studies. This review gives guidance to statistical analysis of the typically complex exposure, co-variate, and effect relationships in human biomonitoring studies.

Published
2020

40. The hCOMET project: International database comparison of results with the comet assay in human biomonitoring. Baseline frequency of DNA damage and effect of main confounders

Author

Milić, Mirta, primary, Ceppi, Marcello, additional, Bruzzone, Marco, additional, Azqueta, Amaya, additional, Brunborg, Gunnar, additional, Godschalk, Roger, additional, Koppen, Gudrun, additional, Langie, Sabine, additional, Møller, Peter, additional, Teixeira, João Paulo, additional, Alija, Avdulla, additional, Anderson, Diana, additional, Andrade, Vanessa, additional, Andreoli, Cristina, additional, Asllani, Fisnik, additional, Bangkoglu, Ezgi Eyluel, additional, Barančoková, Magdalena, additional, Basaran, Nursen, additional, Boutet-Robinet, Elisa, additional, Buschini, Annamaria, additional, Cavallo, Delia, additional, Costa Pereira, Cristiana, additional, Costa, Carla, additional, Costa, Solange, additional, Da Silva, Juliana, additional, Del Boˊ, Cristian, additional, Dimitrijević Srećković, Vesna, additional, Djelić, Ninoslav, additional, Dobrzyńska, Malgorzata, additional, Duračková, Zdenka, additional, Dvořáková, Monika, additional, Gajski, Goran, additional, Galati, Serena, additional, García Lima, Omar, additional, Giovannelli, Lisa, additional, Goroshinskaya, Irina A., additional, Grindel, Annemarie, additional, Gutzkow, Kristine B., additional, Hernández, Alba, additional, Hernández, Carlos, additional, Holven, Kirsten B., additional, Ibero-Baraibar, Idoia, additional, Ottestad, Inger, additional, Kadioglu, Ela, additional, Kažimirová, Alena, additional, Kuznetsova, Elena, additional, Ladeira, Carina, additional, Laffon, Blanca, additional, Lamonaca, Palma, additional, Lebailly, Pierre, additional, Louro, Henriqueta, additional, Mandina Cardoso, Tania, additional, Marcon, Francesca, additional, Marcos, Ricard, additional, Moretti, Massimo, additional, Moretti, Silvia, additional, Najafzadeh, Mojgan, additional, Nemeth, Zsuzsanna, additional, Neri, Monica, additional, Novotna, Bozena, additional, Orlow, Irene, additional, Paduchova, Zuzana, additional, Pastor, Susana, additional, Perdry, Hervé, additional, Spremo-Potparević, Biljana, additional, Ramadhani, Dwi, additional, Riso, Patrizia, additional, Rohr, Paula, additional, Rojas, Emilio, additional, Rossner, Pavel, additional, Safar, Anna, additional, Sardas, Semra, additional, Silva, Maria João, additional, Sirota, Nikolay, additional, Smolkova, Bozena, additional, Staruchova, Marta, additional, Stetina, Rudolf, additional, Stopper, Helga, additional, Surikova, Ekaterina I., additional, Ulven, Stine M., additional, Ursini, Cinzia Lucia, additional, Valdiglesias, Vanessa, additional, Valverde, Mahara, additional, Vodicka, Pavel, additional, Volkovova, Katarina, additional, Wagner, Karl-Heinz, additional, Živković, Lada, additional, Dušinská, Maria, additional, Collins, Andrew R., additional, and Bonassi, Stefano, additional

Published
2021
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42. Influence of the microenvironment on the modulation of the host response by the typhoid toxin

Author

Martin, Océane C.B., primary, Butter, Deborah, additional, Paparouna, Eleni, additional, Theodorou, Sofia D.P., additional, Haykal, Maria M., additional, Boutet-Robinet, Elisa, additional, Tebaldi, Toma, additional, Bergonzini, Anna, additional, Chiloeches, Maria Lopez, additional, Wakeham, Andrew, additional, Rhen, Mikael, additional, Gorgoulis, Vassilis G., additional, Mak, Tak, additional, Pateras, Ioannis S., additional, and Frisan, Teresa, additional

Published
2020
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43. Versicolorin A, a precursor in aflatoxins biosynthesis, is a food contaminant toxic for human intestinal cells

Author

Gauthier, Thierry, primary, Duarte-Hospital, Carolina, additional, Vignard, Julien, additional, Boutet-Robinet, Elisa, additional, Sulyok, Michael, additional, Snini, Selma P., additional, Alassane-Kpembi, Imourana, additional, Lippi, Yannick, additional, Puel, Sylvie, additional, Oswald, Isabelle P., additional, and Puel, Olivier, additional

Published
2020
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44. Application of the comet assay in human biomonitoring: An hCOMET perspective

Author

Azqueta, Amaya, primary, Ladeira, Carina, additional, Giovannelli, Lisa, additional, Boutet-Robinet, Elisa, additional, Bonassi, Stefano, additional, Neri, Monica, additional, Gajski, Goran, additional, Duthie, Susan, additional, Del Bo’, Cristian, additional, Riso, Patrizia, additional, Koppen, Gudrun, additional, Basaran, Nursen, additional, Collins, Andrew, additional, and Møller, Peter, additional

Published
2020
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46. Nongenotoxic 3-Nitroimidazo[1,2- a ]pyridines Are NTR1 Substrates That Display Potent in Vitro Antileishmanial Activity

Author

Fersing, Cyril, Basmaciyan, Louise, Boudot, Clotilde, Pedron, Julien, Hutter, Sébastien, Cohen, Anita, Castera-Ducros, Caroline, Primas, Nicolas, Laget, Michèle, Casanova, Magali, Bourgeade-Delmas, Sandra, Piednoel, Meĺanie, Sournia-Saquet, Alix, Belle Mbou, Valère, Courtioux, Bertrand, Boutet-Robinet, Elisa, Since, Marc, Milne, Rachel, Wyllie, Susan, Fairlamb, Alan, Valentin, Alexis, Rathelot, Pascal, Verhaeghe, Pierre, Vanelle, Patrice, Azas, Nadine, Institut de Chimie Radicalaire (ICR), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), CHU Limoges, Université de Limoges (UNILIM), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), University of Dundee, Membranes et cibles thérapeutiques (MCT), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Biomédicale des Armées (IRBA), Aix Marseille Université (AMU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Contaminants & Stress Cellulaire (ToxAlim-COMICS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT), and Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN)

Subjects
nitroaromatic, Ames test, Ames, imidazopyridine, test, comet assay, nitroreductases, [SDV]Life Sciences [q-bio], parasitic diseases, Leishmania ssp, [CHIM.THER]Chemical Sciences/Medicinal Chemistry
Abstract

International audience; Twenty nine original 3-nitroimidazo[1,2-a]-pyridine derivatives, bearing a phenylthio (or benzylthio) moiety at position 8 of the scaffold, were synthesized. In vitro evaluation highlighted compound 5 as an antiparasitic hit molecule displaying low cytotoxicity for the human HepG2 cell line (CC 50 > 100 μM) alongside good antileishmanial activities (IC 50 = 1−2.1 μM) against L. donovani, L. infantum, and L. major; and good antitrypanosomal activities (IC 50 = 1.3−2.2 μM) against T. brucei brucei and T. cruzi, in comparison to several reference drugs such as miltefosine, fexinidazole, eflornithine, and benznidazole (IC 50 = 0.6 to 13.3 μM). Molecule 5, presenting a low reduction potential (E°= −0.63 V), was shown to be selectively bioactivated by the L. donovani type 1 nitroreductase (NTR1). Importantly, molecule 5 was neither mutagenic (negative Ames test), nor genotoxic (negative comet assay), in contrast to many other nitroaromatics. Molecule 5 showed poor microsomal stability; however, its main metabolite (sulfoxide) remained both active and nonmutagenic, making 5 a good candidate for further in vivo studies.

Published
2018

48. DNA repair as a human biomonitoring tool:Comet assay approaches

Author

Azqueta, Amaya, Langie, Sabine A. S., Boutet-Robinet, Elisa, Duthie, Susan, Ladeira, Carina, Møller, Peter, Collins, Andrew R., Godschalk, Roger W. L., Azqueta, Amaya, Langie, Sabine A. S., Boutet-Robinet, Elisa, Duthie, Susan, Ladeira, Carina, Møller, Peter, Collins, Andrew R., and Godschalk, Roger W. L.

Published
2019

49. A French crop-exposure matrix for use in epidemiological studies on pesticides: PESTIMAT

Author

Baldi, Isabelle, Carles, Camille, Blanc-Lapierre, Audrey, Fabbro-Peray, Pascale, Druet-Cabanac, Michel, Boutet-Robinet, Elisa, Soulat, Jean-Marc, Bouvier, Ghislaine, Lebailly, Pierre, Group, The PESTIMAT, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], BESPIM, Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Neuroépidémiologie Tropicale (NET), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Cancers et préventions, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Contaminants & Stress Cellulaire (ToxAlim-COMICS), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), and The study was supported by grants from the Agence Nationale de la Recherche (ANR), and the Institut National du Cancer (INCA, Canceropole Grand Sud-Ouest).

Subjects
Crops, Agricultural, medicine.medical_specialty, Databases, Factual, Epidemiology, occupational exposures, Health protection, Toxicology, Crop, 03 medical and health sciences, exposure matrix, 0302 clinical medicine, Occupational Exposure, Surveys and Questionnaires, Environmental health, Humans, Medicine, 030212 general & internal medicine, Duration (project management), agriculture, Exposure assessment, [SDV.EE]Life Sciences [q-bio]/Ecology, environment, 2. Zero hunger, business.industry, Public Health, Environmental and Occupational Health, Environmental Exposure, pesticides, Pesticide, crops, 030210 environmental & occupational health, Pollution, Agriculture, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Environmental Pollutants, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Christian ministry, France, Epidemiologic Methods, business, Environmental Monitoring
Abstract

International audience; Pesticide exposure assessment is a key methodological issue for epidemiological studies. The history of pesticide has proven difficult to obtain from individuals' report because of the wide range of active ingredients (AIs). We developed a crop-exposure matrix, which intends to reconstitute parameters of pesticide exposure in France since 1950. PESTIMAT is composed of tables crossing crops and AIs by year and providing the following metrics: (1) probability (proportion of farmers having used the AIs); (2) frequency (number of treatment days); and (3) intensity (application rate of the AIs in kg/ha). Metrics were obtained by the combination of six sources: (i) registration information from the Agriculture Ministry; (ii) information from agricultural bodies on products marketed; (iii) agricultural recommendations by the Plant Health Protection body; (iv) treatment calendars provided by farmers; (v) data from associations of farmers; and (vi) data from the industry. To date, 529 AIs usable between 1950 and 2010 are included in PESTIMAT: 160 fungicides; 160 herbicides; and 209 insecticides. When combined with duration and determinants of intensity, the metrics in PESTIMAT will make it possible to calculate exposure scores and to search for dose-effect relationships, an important criterion for causality judgment in epidemiology.

Published
2015

50. New nitroaromatic candidats for trypanosomiasis therapeutics

Author

Boudot, Clotilde, Fersing, Cyril, Pedron, Julien, Mbou, Valere Belle, Castera-Ducros, Caroline, Primas, Nicolas, Cohen, Anita, Hutter, Sebastien, Bourgeade-Delmas, Sandra, Laget, Michèle, Boutet-Robinet, Elisa, Sournia-Saquet, Alix, Moreau, Alain, Azas, Nadine, Rathelot, Pascal, Vanelle, Patrice, Valentin, Alexis, Verhaeghe, Pierre, Courtioux, Bertrand, Neuroépidémiologie Tropicale (NET), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Chimie Radicalaire (ICR), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques (IP-TPT), Service de Santé des Armées-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Aix Marseille Université (AMU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Contaminants & Stress Cellulaire (ToxAlim-COMICS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Service de Santé des Armées, Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Université de Toulouse (UT)

Subjects
nitroreductases, parasitic diseases, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, nitroaromatic drugs, African Trypanosomiasis
Abstract

International audience; African Trypanosomiasis is a neglected tropical disease, endemic in nearly 30 countries in sub-Saharan Africa. Trypanosoma brucei, the infectious agent responsible for the disease, is transmitted by the bite of Glossina (tsetse fly) and can affect both animals (AAT - Animal African Trypanosomiasis) and humans (HAT - Human African Trypanosomiasis). Without treatment, the disease is fatal. The current therapeutic care is complex and depends on trypanosome species, host and stage of the disease. Therefore, it is essential to find new treatments. In recent years, nitroaromatic compounds present a renewed interest as anti-infective agents like fexinidazole.Some studies show that their antiparasitic activity is based on their selective reduction by parasite nitroreductases (NTR). These NTR leading to metabolites that are cytotoxic for the protozoan.The objective of the study is to develop new nitroaromatic drugs efficient against Trypanosoma.Our collaboration between chemists and biologists allows to synthetize different molecules and test them on various biological models. Firstly, about 200 molecules belonging to the 8-nitroquinolin-2(1H)-one series and 3-nitroimidazo[1,2-a]pyridine series were synthetized. Secondly, in vitro evaluations were performed for all molecules on a HepG2 human cell line, and on a strain of T. b. brucei to evaluate the CC50 and IC50 respectively. In vitro pharmacokinetic tests and comet assays completed the data for the most promising molecules. The four best candidates were included in an in vivo test on a murine model of mice infected by T. b. brucei (strain AnTat 1.1E): briefly, the 4 molecules were tested to evaluate their ability to cross the blood brain barrier, their toxicity and their activity. At the end of the study, an anatomopathological analysis was performed to ensure the absence of damage on vital organs (brain, heart, kidney, liver). The finality of this project is to develop new drug candidates for human and animal therapeutic.

Published
2018

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