35 results on '"H Derradji"'
Search Results
2. Joint research towards a better radiation protection—highlights of the Fifth MELODI Workshop
- Author
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W. Rühm, T. Schneider, Jacques Repussard, Jérémie Dabin, N. Horemans, F. Hardeman, H. Derradji, Lara Struelens, N. R. E. N. Impens, J. Camps, Tanja Perko, Sarah Baatout, M. A. Benotmane, Jean-René Jourdain, Marjan Moreels, Roel Quintens, An Aerts, and Bernd Grosche
- Subjects
Operations research ,business.industry ,Public Health, Environmental and Occupational Health ,General Medicine ,Public relations ,Eurados ,Fifth Melodi Workshop 2013 ,Integrated Research ,Ionising Radiation ,Multidisciplinary European Low Dose Initiative (melodi) ,Neris And Alliance ,Radiation Protection ,Joint research ,Radiation risk ,Preparedness ,Western europe ,Political science ,Strategic research ,Radiation protection ,business ,Waste Management and Disposal ,Waste processing - Abstract
MELODI is the European platform dedicated to low-dose radiation risk research. From 7 October through 10 October 2013 the Fifth MELODI Workshop took place in Brussels, Belgium. The workshop offered the opportunity to 221 unique participants originating from 22 countries worldwide to update their knowledge and discuss radiation research issues through 118 oral and 44 poster presentations. In addition, the MELODI 2013 workshop was reaching out to the broader radiation protection community, rather than only the low-dose community, with contributions from the fields of radioecology, emergency and recovery preparedness, and dosimetry. In this review, we summarise the major scientific conclusions of the workshop, which are important to keep the MELODI strategic research agenda up-to-date and which will serve to establish a joint radiation protection research roadmap for the future.
- Published
- 2014
3. Intérêt de la neuroendoscopie dans l’aménagement des kystes arachnoïdiens intracrâniens
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R. Trad Khoudja, H. Derradji, and M. Nebbal
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Surgery ,Neurology (clinical) - Abstract
Introduction Les kystes arachnoidiens intracrâniens sont des lesions dues a une accumulation anormale de LCR dans certaines localisations cerebrales, en particulier dans la vie embryonnaire. Avec une prevalence relativement faible (1 % des lesions cerebrales intracrâniennes), leur decouverte est souvent fortuite. Cependant, ils peuvent manifester des symptomes cliniques severes ou presenter un risque hemorragique, necessitant une prise en charge neurochirurgicale. L’objectif de notre etude est de demontrer la valeur de l’utilisation de la neuroendoscopie comme technique de choix dans le traitement de ces lesions et de demontrer sa contribution par rapport aux autres techniques neurochirurgicales. Patients et methodes Il s’agit d’une etude prospective et descriptive realisee entre 2012 et 2017 sur 120 patients, âges de quelques jours a 64 ans, presentant des kystes arachnoidiens intracrâniens symptomatiques, dont 100 ont beneficie d’une decompression neurochirurgicale. Les methodes chirurgicales appliquees aux nombres variables sont : fenestration neuroendoscopique, manœuvre et crâniectomie. Les resultats chirurgicaux ont ete evalues sur l’echelle COS (echelle des resultats cliniques) et l’echelle IOA (aspect des resultats de l’imagerie). Resultats La proportion de patients traites par fenestration endoscopique a atteint 81 % du nombre total de patients, en particulier dans les kystes arachnoidiens quadrigeminaux, sellaires et suprasellaires et intraventriculaires, qui ont ete endoscopiquement controles a 100 %. Les autres patients ont beneficie de derivations (10 %), de craniectomies (7 %) et de recreations (2 %). Le taux de complications etait de 16 % du nombre total de patients operes. La neuroendoscopie presentait le taux le plus faible (5 %) par rapport aux autres techniques : la derivation (36 %) et la craniectomie (29 %). Une amelioration clinique a ete notee chez 90 % des patients postoperatoires. Radiologiquement, l’amelioration a touche 68 % des patients operes a court et a long terme. Conclusion La fenestration endoscopique a ete utilisee chez la majorite de nos patients. C’est une technique peu invasive avec de nombreux avantages pour le patient. Cela a attenue l’impact de la chirurgie et elargi la gamme des indications. Elle peut etre utilisee seule ou associee a d’autres techniques en fonction de la localisation et des particularites de chaque kyste. Au vu des resultats obtenus dans notre etude, cette technique a reussi a resoudre le probleme des kystes arachnoidiens profonds d’un cote et a participer largement a la gestion d’autres localisations.
- Published
- 2019
4. Biodegradability of Packaging Materials: Quantitative Evaluation by an Automated Respirometric Method Applied to their Insoluble Constituents as Starch
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Y. Couturier, H. Derradji, and G. Bureau
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Chromatography ,Materials science ,Starch ,Mechanical Engineering ,chemistry.chemical_element ,Biomass ,General Chemistry ,Biodegradation ,Respirometry ,chemistry.chemical_compound ,chemistry ,Volume (thermodynamics) ,Bioreactor ,General Materials Science ,Aeration ,Carbon - Abstract
An automated headspace method to measure the CO 2 evolved is described and developed into a biodegradation test procedure for insoluble substrates. The test system consists of a bioreactor with a working volume of 1.51, fitted with temperature, pH and dissolved oxygen partial pressure control. These parameters enable us to work at the optimal growth conditions for Bacillus amylolicheniformis MIR-41. The study was carried out under continuous aerated conditions at 0.5 and 1.0 v.v.m. Glucose was used as a reference compound because it is completely assimilated by Bacillus amylolicheniformis MIR-41. The percentage of carbon converted into CO 2 was the parameter used to determine the optimal aeration conditions for the biodegradability of wheat starch, a possible packaging material component. The present method was adapted to insoluble substrates at high concentrations for the first time. The reliability of this method was tested by simultaneous measurement of the biomass produced. The carbon content of the biomass is closely correlated with the carbon of the evolved CO 2 . It was also found that production of α-amylase was correlated with CO 2 evolution during exponential growth. Finally, these study validates CO 2 measurement as an assessment of the extent of biodegradation of insoluble substrates, even at high concentrations.
- Published
- 1996
5. Cytometric methods to analyze radiation effects
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S, Baatout and H, Derradji
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Chromosome Aberrations ,Eukaryotic Cells ,Micronucleus Tests ,Cell Cycle ,Cytological Techniques ,Animals ,Humans ,Apoptosis ,Comet Assay ,Cytophotometry ,DNA ,Flow Cytometry ,In Situ Hybridization, Fluorescence - Abstract
Here, we review the most relevant cytometric methods currently used to analyze ionizing radiation effects. Particular interest has been devoted to the following methods: chromosomal aberrations, micronucleus assay, fluorescence in situ hybridization chromosome painting, comet assay, comet-FISH assay as well as flow cytometry.
- Published
- 2004
6. A biogradable starch based coating to waterproof hydrophilic materials
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H. Derradji, C. Fringant, M. Rinaudo, S. Guilbert, N. Gontard, Université de Montpellier (UM), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)
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Paper sheet ,Coated paper ,Materials science ,Starch ,Organic Chemistry ,Kinetics ,food and beverages ,Chemical modification ,Biodegradation ,Polyethylene ,engineering.material ,chemistry.chemical_compound ,[CHIM.POLY]Chemical Sciences/Polymers ,chemistry ,Coating ,Chemical engineering ,Polymer chemistry ,engineering ,[SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering ,ComputingMilieux_MISCELLANEOUS ,Food Science - Abstract
In this work, the efficiency of starch acetylation to reduce water sensitivity of hydrophilic materials was investigated. Starch acetate was either included in foamed starch trays and/or used to coat these trays, wheat gluten based films or paper sheets. The water sensitivity of these foamed trays (quantity and kinetics of water uptake) is shown to decrease when starch acetate content of the foam increases. The coating of the hydrophilic trays with starch triacetate is detailled. The biodegradability of the coating was also unambigously demonstrated. Whatever the nature of the foam, the coating allowed in all cases to slow down the water uptake but best results were obtained in the case of a coated foam prepared with a starch-starch acetate blend. The coating of wheat gluten films was tested with disappointing results because of chemical incompatibility between wheat gluten and starch acetate. In the case of paper sheet coating, the efficiency in water sensitivity reduction increased with the thickness of the coating film. However, the water sensitivity of this coated paper remained higher than paper coated with polyethylene (with a similar coating thickness).
7. Joint research towards a better radiation protection—highlights of the Fifth MELODI Workshop.
- Author
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A M Aerts, N R E N Impens, S Baatout, M A Benotmane, J Camps, J M Dabin, H Derradji, N Horemans, M Moreels, T Perko, R Quintens, L Struelens, F Hardeman, B Grosche, J-R Jourdain, J Repussard, W Rühm, and T Schneider
- Subjects
RADIATION protection ,RADIATION doses ,FUKUSHIMA Nuclear Accident, Fukushima, Japan, 2011 ,RADIATION & the environment ,RADIATION damage ,CONFERENCES & conventions - Abstract
MELODI is the European platform dedicated to low-dose radiation risk research. From 7 October through 10 October 2013 the Fifth MELODI Workshop took place in Brussels, Belgium. The workshop offered the opportunity to 221 unique participants originating from 22 countries worldwide to update their knowledge and discuss radiation research issues through 118 oral and 44 poster presentations. In addition, the MELODI 2013 workshop was reaching out to the broader radiation protection community, rather than only the low-dose community, with contributions from the fields of radioecology, emergency and recovery preparedness, and dosimetry. In this review, we summarise the major scientific conclusions of the workshop, which are important to keep the MELODI strategic research agenda up-to-date and which will serve to establish a joint radiation protection research roadmap for the future. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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8. Modulation of VEGF Expression and Oxidative Stress Response by Iodine Deficiency in Irradiated Cancerous and Non-Cancerous Breast Cells.
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Vanderstraeten J, Baselet B, Buset J, Ben Said N, de Ville de Goyet C, Many MC, Gérard AC, and Derradji H
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- Antioxidants metabolism, Cell Line, Tumor, Dose-Response Relationship, Drug, Female, Humans, MCF-7 Cells, Neovascularization, Pathologic, RNA, Messenger metabolism, Reactive Oxygen Species metabolism, Up-Regulation, Breast metabolism, Breast radiation effects, Breast Neoplasms metabolism, Breast Neoplasms radiotherapy, Iodine deficiency, Oxidative Stress, Vascular Endothelial Growth Factor A metabolism
- Abstract
Breast cancer remains a major concern and its physiopathology is influenced by iodine deficiency (ID) and radiation exposure. Since radiation and ID can separately induce oxidative stress (OS) and microvascular responses in breast, their combination could additively increase these responses. Therefore, ID was induced in MCF7 and MCF12A breast cell lines by medium change. Cells were then X-irradiated with doses of 0.05, 0.1, or 3 Gy. In MCF12A cells, both ID and radiation (0.1 and 3 Gy) increased OS and vascular endothelial growth factor (VEGF) expression, with an additive effect when the highest dose was combined with ID. However, in MCF7 cells no additive effect was observed. VEGF mRNA up-regulation was reactive oxygen species (ROS)-dependent, involving radiation-induced mitochondrial ROS. Results on total VEGF mRNA hold true for the pro-angiogenic isoform VEGF165 mRNA, but the treatments did not modulate the anti-angiogenic isoform VEGF165b. Radiation-induced antioxidant response was differentially regulated upon ID in both cell lines. Thus, radiation response is modulated according to iodine status and cell type and can lead to additive effects on ROS and VEGF. As these are often involved in cancer initiation and progression, we believe that iodine status should be taken into account in radiation prevention policies.
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- 2020
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9. Acute iodine deficiency induces a transient VEGF-dependent microvascular response in mammary glands involving HIF-1, ROS, and mTOR.
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Vanderstraeten J, Derradji H, Sonveaux P, Colin IM, Many MC, and Gérard AC
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- Acetylcysteine metabolism, Animals, Antioxidants metabolism, Breast metabolism, Cell Line, Tumor, Female, Humans, Lactation metabolism, MCF-7 Cells, Mammary Glands, Animal metabolism, Mice, Receptors, Vascular Endothelial Growth Factor metabolism, Signal Transduction physiology, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Iodine deficiency, Mammary Glands, Human metabolism, Microvessels metabolism, Reactive Oxygen Species metabolism, TOR Serine-Threonine Kinases metabolism, Vascular Endothelial Growth Factor A metabolism
- Abstract
Iodine deficiency (ID), which affects almost two billion people worldwide, is associated with breast pathologies such as fibrosis in human and induces breast atypia in animal models. Because ID induces vascular activation in the thyroid, another iodide-uptaking organ, and as breast is also sensitive to ID, we aimed to characterize ID-induced effects on the breast microvasculature in vivo and in two different breast cell lines in vitro. Virgin and lactating NMRI mice received an iodide-deficient diet and a Na
+ /I- symporter inhibitor for 1 to 20 days. Some virgin mice were treated with vascular endothelial growth factor A (VEGF) or VEGF receptor inhibitors. In vitro, ID was induced in MCF7 and MCF12A cells by replacing the iodide-containing medium by an iodide-deficient medium. In vivo, VEGF expression was increased following ID in mammary tissues. Consequently, ID induced a transient increase in mammary gland blood flow, measured after anesthesia, in virgin and lactating mice, which was repressed by VEGF or VEGF receptor inhibitors. In MCF7 cells, ID induced a transient increase in reactive oxygen species, followed by an increase in hypoxia-inducible factor-1α (HIF-1α) protein and VEGF mRNA expression. Antioxidant N-acetylcysteine and mammalian target of rapamycin (mTOR) inhibitor blocked ID-induced HIF-1α protein increase and VEGF transcription. However, mTOR activity was not inhibited by N-acetylcysteine. Similar responses were observed in MCF12A cells. These data indicate that ID activates the canonical VEGF pathway and mTOR in breast tissues, which provides new insights to better understand the correlation between ID, vascular activation, and breast pathologies.- Published
- 2018
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10. Iodine deficiency induces a VEGF-dependent microvascular response in salivary glands and in the stomach.
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Vanderstraeten J, Derradji H, Craps J, Sonveaux P, Colin IM, Many MC, and Gérard AC
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- Animals, Blotting, Western, Disease Models, Animal, Fluorescent Antibody Technique, Iodine deficiency, Mice, Salivary Glands blood supply, Sodium metabolism, Stomach blood supply, Gastric Mucosa metabolism, Iodine metabolism, Microvessels, Salivary Glands metabolism, Symporters metabolism, Vascular Endothelial Growth Factor A metabolism
- Abstract
Despite efforts to optimize iodine supply in iodine deficient countries, iodine deficiency (ID) remains a global problem worldwide. Activation of the local microvasculature by ID in the thyroid gland aims at improving the local supply of iodide. For this purpose, the thyrocytes secrete vascular endothelial growth factor (VEGF) that acts on adjacent capillaries, via a reactive oxygen species (ROS)/Hypoxia Inducible factor (HIF)-dependent pathway. Beside the thyroid, other organs including salivary glands and the stomach do express the sodium/iodide symporter (NIS) and are able to take iodide up, potentially rendering them sensitive to ID. To verify this hypothesis, ID-induced effects on the local microvasculature were studied in salivary glands and in the stomach. ID was induced by feeding young mice with an iodide-deficient diet and NIS inhibitor perchlorate in the drinking water. In salivary glands, ID induced a transient increase in HIF-1α protein expression accompanied by a transient, VEGF-dependent increase in blood flow. In the gastric mucosa, ID transiently increased VEGF expression in the mucin-secreting epithelium and in ghrelin-secreting endocrine cells. These observations suggest that microvascular changes in response to ID occur in NIS-expressing tissues other than the thyroid. NIS expressing cells could be viewed as iodide sensors that respond to ID by inducing vascular changes, probably to optimize iodide bioavailability at regional or systemic levels.
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- 2016
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11. Joint research towards a better radiation protection-highlights of the Fifth MELODI Workshop.
- Author
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Aerts AM, Impens NR, Baatout S, Benotmane MA, Camps J, Dabin JM, Derradji H, Grosche B, Horemans N, Jourdain JR, Moreels M, Perko T, Quintens R, Repussard J, Rühm W, Schneider T, Struelens L, and Hardeman F
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- Europe, Humans, Risk Management methods, Biomedical Research trends, Radiation Injuries prevention & control, Radiation Monitoring methods, Radiation Protection methods, Radioactive Hazard Release prevention & control
- Abstract
MELODI is the European platform dedicated to low-dose radiation risk research. From 7 October through 10 October 2013 the Fifth MELODI Workshop took place in Brussels, Belgium. The workshop offered the opportunity to 221 unique participants originating from 22 countries worldwide to update their knowledge and discuss radiation research issues through 118 oral and 44 poster presentations. In addition, the MELODI 2013 workshop was reaching out to the broader radiation protection community, rather than only the low-dose community, with contributions from the fields of radioecology, emergency and recovery preparedness, and dosimetry. In this review, we summarise the major scientific conclusions of the workshop, which are important to keep the MELODI strategic research agenda up-to-date and which will serve to establish a joint radiation protection research roadmap for the future.
- Published
- 2014
- Full Text
- View/download PDF
12. Iodine-deficiency-induced long lasting angiogenic reaction in thyroid cancers occurs via a vascular endothelial growth factor-hypoxia inducible factor-1-dependent, but not a reactive oxygen species-dependent, pathway.
- Author
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Gérard AC, Humblet K, Wilvers C, Poncin S, Derradji H, de Ville de Goyet C, Abou-el-Ardat K, Baatout S, Sonveaux P, Denef JF, and Colin IM
- Subjects
- Animals, Carcinoma blood supply, Cell Line, Tumor, Deficiency Diseases complications, Deficiency Diseases metabolism, Humans, Laser-Doppler Flowmetry, Mice, Mice, Transgenic, Neovascularization, Pathologic etiology, Neovascularization, Pathologic metabolism, RNA, Messenger analysis, Reactive Oxygen Species metabolism, Symporters metabolism, Thyroid Gland blood supply, Thyroid Gland diagnostic imaging, Thyroid Neoplasms blood supply, Thyroid Neoplasms diagnostic imaging, Ultrasonography, Carcinoma metabolism, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Iodine deficiency, Thyroid Neoplasms metabolism, Vascular Endothelial Growth Factor A metabolism
- Abstract
Background: In the thyroid, iodine deficiency (ID) induces angiogenesis via a tightly controlled reactive oxygen species (ROS)-hypoxia inducible factor-1 (HIF-1)-vascular endothelial growth factor (VEGF) dependent pathway (ROS-HIF-VEGF). Deficient iodine intake may be associated with increased thyroid cancer incidence. The hypothesis of this work is to test whether ID affects the angiogenic processes in thyroid malignant cells by altering the ROS-HIF-VEGF pathway., Methods: Goiters were obtained in RET/PTC3 transgenic and wild-type (wt) mice and ID was induced in three thyroid carcinoma cell lines (TPC-1, 8305c, and R082-w1). Thyroid blood flow, VEGF mRNA and protein, and HIF-1α protein expression were measured. The role of HIF-1 and of ROS was assessed using echinomycin and N-acetylcysteine (NAC), respectively., Results: The goitrogen treatment increased the thyroid blood flow in wt and RET/PTC3 mice. Compared with wt mice, basal VEGF expression was higher in RET/PTC3 mice and increased with goitrogen treatment. In the three cell lines, ID induced marked increases in VEGF mRNA, and moderate increases in HIF-1α protein expression that were not transient as in normal cells. ID-induced VEGF mRNA expression was fully (8305c), partially (TPC-1), or not (R082-w1) blocked by echinomycin. NAC had no effect on ID-induced VEGF mRNA and HIF-1α protein expression in the three cell lines., Conclusions: ID induces a long lasting angiogenic phenotype in thyroid cancer cells that occurs through VEGF induction via a pathway partially mediated by HIF-1, but not by ROS. These results suggest that, in contrast with normal cells, ID-induced angiogenesis in cancer cells occurs via alternative and likely less controlled routes, thereby leading to uncontrolled growth.
- Published
- 2012
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13. Low dose irradiation of thyroid cells reveals a unique transcriptomic and epigenetic signature in RET/PTC-positive cells.
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Abou-El-Ardat K, Monsieurs P, Anastasov N, Atkinson M, Derradji H, De Meyer T, Bekaert S, Van Criekinge W, and Baatout S
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- Animals, Cell Line, Cell Line, Tumor, Dose-Response Relationship, Radiation, Gene Expression, Humans, Mice, Mice, Inbred C57BL, MicroRNAs metabolism, Thyroid Neoplasms metabolism, X-Rays, Oncogene Proteins, Fusion metabolism, Protein-Tyrosine Kinases metabolism, RNA Processing, Post-Transcriptional, Thyroid Gland radiation effects, Thyroid Neoplasms genetics
- Abstract
The high doses of radiation received in the wake of the Chernobyl incident and the atomic bombing of Hiroshima and Nagasaki have been linked to the increased appearance of thyroid cancer in the children living in the vicinity of the site. However, the data gathered on the effect of low doses of radiation on the thyroid remain limited. We have examined the genome wide transcriptional response of a culture of TPC-1 human cell line of papillary thyroid carcinoma origin with a RET/PTC1 translocation to various doses (0.0625, 0.5, and 4Gy) of X-rays and compared it to response of thyroids with a RET/PTC3 translocation and against wild-type mouse thyroids irradiated with the same doses using Affymetrix microarrays. We have found considerable overlap at a high dose of 4Gy in both RET/PTC-positive systems but no common genes at 62.5mGy. In addition, the response of RET/PTC-positive system at all doses was distinct from the response of wild-type thyroids with both systems signaling down different pathways. Analysis of the response of microRNAs in TPC-1 cells revealed a radiation-responsive signature of microRNAs in addition to dose-responsive microRNAs. Our results point to the fact that a low dose of X-rays seems to have a significant proliferative effect on normal thyroids. This observation should be studied further as opposed to its effect on RET/PTC-positive thyroids which was subtle, anti-proliferative and system-dependent., (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Published
- 2012
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14. Stress response and humoral immune system alterations related to chronic hypergravity in mice.
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Guéguinou N, Bojados M, Jamon M, Derradji H, Baatout S, Tschirhart E, Frippiat JP, and Legrand-Frossi C
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- Animals, Anxiety complications, Atrophy pathology, Biomarkers blood, Body Weight, Corticosterone blood, Cytokines blood, Disease Models, Animal, Humans, Immunoglobulins blood, Lymphocyte Activation, Male, Mice, Mice, Inbred C57BL, Spleen pathology, Stress, Psychological psychology, Thymus Gland pathology, Anxiety immunology, Anxiety metabolism, Hypergravity adverse effects, Stress, Psychological immunology, Stress, Psychological metabolism
- Abstract
Spaceflights are known to induce stress and immune dysregulation. Centrifugation, as hindlimb unloading, is a good ground based-model to simulate altered gravity which occurs during space missions. The aim of this study was to investigate the consequences of a long-term exposure to different levels of hypergravity on the stress response and the humoral immunity in a mouse model. For this purpose, adult C57Bl/6J male mice were subjected for 21 days either to control conditions or to 2G or 3G acceleration gravity forces. Corticosterone level and anxiety behavior revealed a stress response which was associated with a decrease of body weight, after 21-day of centrifugation at 3G but not at 2G. Spleen lymphocyte lipopolysaccharide (LPS) responsiveness was diminished by 40% in the 2G group only, whereas a decrease was noted when cells were stimulated with concanavalin A for both 2G and 3G groups (about 25% and 20%, respectively) compared to controls. Pro-inflammatory chemokines (MCP-1 and IP-10) and Th1 cytokines (IFNγ and IL2) were slightly decreased in the 2G group and strongly decreased in the 3G mouse group. Regarding Th2 cytokines (IL4, IL5) no further significant modification was observed, whereas the immunosuppressive cytokine IL10 was slightly increased in the 3G mice. Finally, serum IgG concentration was twice higher whereas IgA concentration was slightly increased (about 30%) and IgM were unchanged in 2G mice compared to controls. No difference was observed in the 3G group with these isotypes. Consequently, functional immune dysregulations and stress responses were dependent of the gravity level., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2012
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15. Response to low-dose X-irradiation is p53-dependent in a papillary thyroid carcinoma model system.
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Abou-El-Ardat K, Derradji H, de Vos W, de Meyer T, Bekaert S, van Criekinge W, and Baatout S
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- Biomarkers metabolism, Carcinoma, Carcinoma, Papillary, Caspase 3, Cell Cycle radiation effects, Cell Death drug effects, Cells, Cultured, Cytokines metabolism, DNA Breaks, Double-Stranded radiation effects, Humans, Protein Biosynthesis, Radiotherapy Dosage, Thyroid Cancer, Papillary, Transforming Growth Factor beta1 metabolism, beta-Galactosidase metabolism, Thyroid Neoplasms metabolism, Thyroid Neoplasms radiotherapy, Tumor Suppressor Protein p53 metabolism
- Abstract
The link between high doses of radiation and thyroid cancer has been well established in various studies, as opposed to the effects of low doses. In this study, we investi-gated the effects of low-dose X-ray irradiation in a papillary thyroid carcinoma model with wild-type and mutated p53. A low dose of 62.5 mGy was enough to cause an upregulation of p16 and a decrease in the number of TPC-1 cells in the S phase, but not in the number of BCPAP p53-mutant cells. At a dose of 0.5 Gy, visible signs of senescence appeared only in the TPC-1 cells. We conclude that low doses of X-rays are enough to cause a change in cell cycle distribution, possibly p53-dependent p16 activation, but no significant apoptosis. Senescence requires higher doses of X-irradiation via a mechanism involving both p16 and p21.
- Published
- 2011
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16. Transgenerational developmental effects and genomic instability after X-irradiation of preimplantation embryos: studies on two mouse strains.
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Jacquet P, Buset J, Neefs M, Vankerkom J, Benotmane MA, Derradji H, Hildebrandt G, and Baatout S
- Subjects
- Animals, Embryo, Mammalian radiation effects, Female, Genomic Instability, Mice, Mice, Inbred ICR, Pregnancy, Abnormalities, Radiation-Induced genetics, Blastocyst radiation effects, Embryonic Development radiation effects
- Abstract
Recent results have shown that irradiation of a single cell, the zygote or 1-cell embryo of various mouse strains, could lead to congenital anomalies in the fetuses. In the Heiligenberger strain, a link between the radiation-induced congenital anomalies and the development of a genomic instability was also suggested. Moreover, further studies showed that in that strain, both congenital anomalies and genomic instability could be transmitted to the next generation. The aim of the experiments described in this paper was to investigate whether such non-targeted transgenerational effects could also be observed in two other radiosensitive mouse strains (CF1 and ICR), using lower radiation doses. Irradiation of the CF1 and ICR female zygotes with 0.2 or 0.4Gy did not result in a decrease of their fertility after birth, when they had reached sexual maturity. Moreover, females of both strains that had been X-irradiated with 0.2Gy exhibited higher rates of pregnancy, less resorptions and more living fetuses. Additionally, the mean weight of living fetuses in these groups had significantly increased. Exencephaly and dwarfism were observed in CF1 fetuses issued from control and X-irradiated females. In the control group of that strain, polydactyly and limb deformity were also found. The yields of abnormal fetuses did not differ significantly between the control and X-irradiated groups. Polydactyly, exencephaly and dwarfism were observed in fetuses issued from ICR control females. In addition to these anomalies, gastroschisis, curly tail and open eye were observed at low frequencies in ICR fetuses issued from X-irradiated females. Again, the frequencies of abnormal fetuses found in the different groups did not differ significantly. In both CF1 and ICR mouse strains, irradiation of female zygotes did not result in the development of a genomic instability in the next generation embryos. Overall, our results suggest that, at the moderate doses used, developmental defects observed after X-irradiation of female zygotes of these two sensitive mouse strains should not be transmitted to the next generation. Paradoxically, other studies would be needed to address the question of a potential increase of fertility after doses lower than 0.2Gy in both strains., (Copyright 2010 Elsevier B.V. All rights reserved.)
- Published
- 2010
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17. Medium-mediated DNA repair response after ionizing radiation is correlated with the increase of specific cytokines in human fibroblasts.
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Dieriks B, De Vos WH, Derradji H, Baatout S, and Van Oostveldt P
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- Cell Line, Culture Media, Conditioned, DNA-Binding Proteins metabolism, HeLa Cells, Histones metabolism, Humans, Up-Regulation, Validation Studies as Topic, X-ray Repair Cross Complementing Protein 1, Cytokines metabolism, DNA Repair, Fibroblasts metabolism, Radiation, Ionizing
- Abstract
Radiation induced bystander effects, either protective or adverse, have been identified in a variety of cells and for different endpoints. They are thought to arise from communication between cells through direct cell-cell contacts and via transmissible molecules secreted into the medium by targeted cells. We have investigated medium-mediated damage response in human dermal fibroblasts (HDF) after exposure to ionizing irradiation. We show that HDF experience an elevated level of double stranded DNA damage repair response when incubated with conditioned growth medium of irradiated cells. The magnitude of this response is much lower than observed for directly irradiated cells and is proportional to the radiation dose, as is its persistence across time. Since secretion of cytokines is one of the possible pathways linking targeted and non-targeted cells a multiplex analysis was performed. Four cytokines - IL6, IL8, MCP-1 and RANTES - were identified in the growth medium of irradiated cells after exposure to X-rays (2Gy). These cytokines were significantly upregulated and each cytokine showed differential upregulation kinetics. Finally we performed a functional analysis to see if IL6 and MCP-1 could induce gammaH2AX foci formation. IL6 caused a significant increase in spot occupancy compared to controls. Although only indicative MCP-1 appears to have the opposite effect as it caused a drop in spot occupancy. The combined addition of these two cytokines produced no significant response was observed. Both IL6 and MCP-1 have an effect on the gammaH2AX spot occupancy possibly linking these cytokines to the bystander response., (Copyright 2010 Elsevier B.V. All rights reserved.)
- Published
- 2010
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18. Ionizing radiation-induced gene modulations, cytokine content changes and telomere shortening in mouse fetuses exhibiting forelimb defects.
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Derradji H, Bekaert S, De Meyer T, Jacquet P, Abou-El-Ardat K, Ghardi M, Arlette M, and Baatout S
- Subjects
- Abnormalities, Radiation-Induced etiology, Abnormalities, Radiation-Induced pathology, Amniotic Fluid metabolism, Animals, Apoptosis, DNA Damage, Female, Fetus abnormalities, Forelimb abnormalities, Limb Buds cytology, Limb Buds radiation effects, MAP Kinase Signaling System radiation effects, Male, Mice, Mice, Inbred C57BL, Telomere metabolism, Tumor Suppressor Protein p53, Abnormalities, Radiation-Induced metabolism, Cytokines metabolism, Fetus metabolism, Forelimb metabolism, Maternal Exposure adverse effects, Telomere ultrastructure
- Abstract
Several lines of evidence have linked limb teratogenesis to radiation-induced apoptosis and to the p53 status in murine fetuses. In previous reports, we studied the occurrence of various malformations after intrauterine irradiation and showed that these malformations were modulated by p53-deficiency as well as by the developmental stage at which embryos were irradiated. In this new study, we focused onto one particular phenotype namely forelimb defects to further unravel the cellular and molecular mechanisms underlying this malformation. We measured various parameters expected to be directly or indirectly influenced by irradiation damage. The mouse fetuses were irradiated at day 12 p.c. (post conception) and examined for forelimb defects on gestational days 15, 16, 17 and 19 of development. The release of inflammatory cytokines was determined in the amniotic fluid on day 16 p.c. and the mean telomere lengths assessed at days 12, 13 and 19 p.c. Differential gene expression within the forelimb bud tissues was determined using Real Time quantitative PCR (RTqPCR) 24 h following irradiation. Apoptosis was investigated in the normal and malformed fetuses using the TUNEL assay and RTqPCR. First, we found that irradiated fetuses with forelimb defects displayed excessive apoptosis in the predigital regions. Besides, overexpression of the pro-apoptotic Bax gene indicates a mitochondrial-mediated cell death. Secondly, our results showed overexpression of MKK3 and MKK7 (members of the stress-activated MAP kinase family) within the malformed fetuses. The latter could be involved in radiation-induced apoptosis through activation of the p38 and JNK pathways. Thirdly, we found that irradiated fetuses exhibiting forelimb defects showed a marked telomere shortening. Interestingly, telomere shortening was observed as the malformations became apparent. Fourthly, we measured cytokine levels in the amniotic fluid and detected a considerable inflammatory reaction among the irradiated fetuses as evidenced by the increase in pro-inflammatory cytokine levels. Altogether, our data suggest that transcriptional modulations of apoptotic, inflammation, stress, and DNA damage players are early events in radiation-induced forelimb defects. These changes resulted in harsh developmental conditions as indicated by a marked increase in cytokine levels in the amniotic fluid and telomere shortening, two features concomitant with the onset of the forelimb defect phenotype in our study.
- Published
- 2008
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19. Effects of basic fibroblast growth factor on endothelial cells under conditions of simulated microgravity.
- Author
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Ulbrich C, Westphal K, Baatout S, Wehland M, Bauer J, Flick B, Infanger M, Kreutz R, Vadrucci S, Egli M, Cogoli A, Derradji H, Pietsch J, Paul M, and Grimm D
- Subjects
- Cells, Cultured, Cytokines, Endothelial Cells metabolism, Humans, NF-kappa B p50 Subunit, Nitric Oxide Synthase Type III, Transcription Factor RelA, Apoptosis, Endothelial Cells pathology, Fibroblast Growth Factor 2 pharmacology, Weightlessness adverse effects
- Abstract
Fibroblast growth factors interact with appropriate endothelial cell (EC) surface receptors and initiate intracellular signal cascades, which participate in modulating blood vessel growth. EC, upon exposure to basic fibroblast growth factors (bFGFs) undergo profound functional alterations, which depend on their actual sensitivity and involve gene expression and de novo protein synthesis. We investigated the effects of bFGF on signaling pathways of EA.hy926 cells in different environments. EC were cultured under normal gravity (1 g) and simulated microgravity (micro g) using a three-dimensional (3D) clinostat. Microgravity induced early and late apoptosis, extracellular matrix proteins, endothelin-1 (ET-1) and TGF-beta(1) expression. Microgravity reduced eNOS mRNA within 24 h. Moreover, a six- to eightfold higher amount of IL-6 and IL-8 was secreted within 24 h micro g. In addition, microgravity induced a duplication of NF-kappaB p50, while p65 was quadrupled. At 1 g, bFGF application (4 h) reduced ET-1, TGF-beta(1) and eNOS gene expression. After 24 h, bFGF enhanced fibronectin, VEGF, Flk-1, Flt-1, the release of IL-6, IL-8, and TGF-beta(1). Furthermore, bFGF promoted apoptosis, reduced NFkB p50, but enhanced NFkB p65. After 4 h micro g, bFGF decreased TGF-beta(1), eNOS, and ET-1 gene expression. After 24 h micro g, bFGF elevated fibronectin, Flk-1 and Flt-1 protein, and reduced IL-6 and IL-8 compared with vehicle treated micro g cultures. In micro g, bFGF enhanced NF-KappaB p50 by 50%, Bax by 25% and attenuated p65, activation of caspase-3 and annexin V-positive cells. bFGF differently changes intracellular signals in ECs depending whether it is applied under microgravity or normal gravity conditions. In microgravity, bFGF contributes to protect the EC from apoptosis., (2008 Wiley-Liss, Inc.)
- Published
- 2008
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20. Effects of simulated space conditions on foetal mouse fibroblasts.
- Author
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Beck M, Hautefelt J, Jacquet P, Derradji H, Van Oostveldt K, Buset J, Neefs M, Vanhavere F, Van Oostveldt P, and Baatout S
- Subjects
- Analysis of Variance, Animals, Caspase 3 metabolism, Cell Cycle physiology, Cell Cycle radiation effects, Dose-Response Relationship, Radiation, Fetus, Fibroblasts cytology, Fibroblasts radiation effects, Humans, Mice, Organogenesis radiation effects, Space Simulation, Fibroblasts physiology, Organogenesis physiology, Weightlessness Simulation
- Published
- 2008
21. Genrisk-T project: response of the TPC-1 papillary thyroid carcinoma cell line to a range of low to high doses of irradiation.
- Author
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Abou-El-Ardat K, Derradji H, Bekaert S, De Meyer T, Van Criekinge W, and Baatout S
- Subjects
- Cell Division radiation effects, Cell Survival radiation effects, Humans, Proto-Oncogene Proteins c-ret, S Phase radiation effects, Carcinoma, Papillary genetics, Dose-Response Relationship, Radiation, Thyroid Neoplasms genetics, Tumor Cells, Cultured radiation effects
- Published
- 2008
22. Modeled gravitational unloading induced downregulation of endothelin-1 in human endothelial cells.
- Author
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Infanger M, Ulbrich C, Baatout S, Wehland M, Kreutz R, Bauer J, Grosse J, Vadrucci S, Cogoli A, Derradji H, Neefs M, Küsters S, Spain M, Paul M, and Grimm D
- Subjects
- Apoptosis physiology, Caspase 3 genetics, Caspase 3 metabolism, Cells, Cultured, Cytokines genetics, Cytokines metabolism, Cytoskeleton metabolism, Cytoskeleton ultrastructure, Down-Regulation, Endothelial Cells cytology, Endothelin-1 genetics, Gene Expression Profiling, Gene Expression Regulation, Humans, Microarray Analysis, Osteopontin genetics, Osteopontin metabolism, Transforming Growth Factor beta1 genetics, Transforming Growth Factor beta1 metabolism, Weightlessness, fas Receptor genetics, fas Receptor metabolism, Endothelial Cells metabolism, Endothelin-1 metabolism, Weightlessness Simulation
- Abstract
Many space missions have shown that prolonged space flights may increase the risk of cardiovascular problems. Using a three-dimensional clinostat, we investigated human endothelial EA.hy926 cells up to 10 days under conditions of simulated microgravity (microg) to distinguish transient from long-term effects of microg and 1g. Maximum expression of all selected genes occurred after 10 min of clinorotation. Gene expression (osteopontin, Fas, TGF-beta(1)) declined to slightly upregulated levels or rose again (caspase-3) after the fourth day of clinorotation. Caspase-3, Bax, and Bcl-2 protein content was enhanced for 10 days of microgravity. In addition, long-term accumulation of collagen type I and III and alterations of the cytoskeletal alpha- and beta-tubulins and F-actin were detectable. A significantly reduced release of soluble factors in simulated microgravity was measured for brain-derived neurotrophic factor, tissue factor, vascular endothelial growth factor (VEGF), and interestingly for endothelin-1, which is important in keeping cardiovascular balances. The gene expression of endothelin-1 was suppressed under microg conditions at days 7 and 10. Alterations of the vascular endothelium together with a decreased release of endothelin-1 may entail post-flight health hazards for astronauts.
- Published
- 2007
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23. Induction of three-dimensional assembly and increase in apoptosis of human endothelial cells by simulated microgravity: impact of vascular endothelial growth factor.
- Author
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Infanger M, Kossmehl P, Shakibaei M, Baatout S, Witzing A, Grosse J, Bauer J, Cogoli A, Faramarzi S, Derradji H, Neefs M, Paul M, and Grimm D
- Subjects
- Cell Line, Collagen Type I metabolism, Collagen Type I ultrastructure, Cytoskeleton chemistry, Cytoskeleton metabolism, Cytoskeleton ultrastructure, Endothelium, Vascular metabolism, Endothelium, Vascular ultrastructure, Extracellular Matrix chemistry, Extracellular Matrix metabolism, Extracellular Matrix ultrastructure, Fibronectins metabolism, Fibronectins ultrastructure, Humans, Keratins metabolism, Keratins ultrastructure, Laminin metabolism, Laminin ultrastructure, Osteopontin, Sialoglycoproteins metabolism, Sialoglycoproteins ultrastructure, Tubulin metabolism, Tubulin ultrastructure, Vascular Endothelial Growth Factor Receptor-2 metabolism, Vascular Endothelial Growth Factor Receptor-2 ultrastructure, Apoptosis drug effects, Endothelium, Vascular cytology, Endothelium, Vascular drug effects, Vascular Endothelial Growth Factor A pharmacology, Weightlessness Simulation instrumentation, Weightlessness Simulation methods
- Abstract
Endothelial cells play a crucial role in the pathogenesis of many diseases and are highly sensitive to low gravity conditions. Using a three-dimensional random positioning machine (clinostat) we investigated effects of simulated weightlessness on the human EA.hy926 cell line (4, 12, 24, 48 and 72 h) and addressed the impact of exposure to VEGF (10 ng/ml). Simulated microgravity resulted in an increase in extracellular matrix proteins (ECMP) and altered cytoskeletal components such as microtubules (alpha-tubulin) and intermediate filaments (cytokeratin). Within the initial 4 h, both simulated microgravity and VEGF, alone, enhanced the expression of ECMP (collagen type I, fibronectin, osteopontin, laminin) and flk-1 protein. Synergistic effects between microgravity and VEGF were not seen. After 12 h, microgravity further enhanced all proteins mentioned above. Moreover, clinorotated endothelial cells showed morphological and biochemical signs of apoptosis after 4 h, which were further increased after 72 h. VEGF significantly attenuated apoptosis as demonstrated by DAPI staining, TUNEL flow cytometry and electron microscopy. Caspase-3, Bax, Fas, and 85-kDa apoptosis-related cleavage fragments were clearly reduced by VEGF. After 72 h, most surviving endothelial cells had assembled to three-dimensional tubular structures. Simulated weightlessness induced apoptosis and increased the amount of ECMP. VEGF develops a cell-protective influence on endothelial cells exposed to simulated microgravity.
- Published
- 2006
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24. About histone H1 phosphorylation during mitosis.
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Baatout S and Derradji H
- Subjects
- Animals, CDC2 Protein Kinase metabolism, Chromatin metabolism, Cyclin B metabolism, Phosphorylation, Protamine Kinase metabolism, Histones metabolism, Mitosis physiology
- Published
- 2006
- Full Text
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25. Telomere shortening is associated with malformation in p53-deficient mice after irradiation during specific stages of development.
- Author
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Bekaert S, Derradji H, De Meyer T, Michaux A, Buset J, Neefs M, Mergeay M, Jacquet P, Van Oostveldt P, and Baatout S
- Subjects
- Animals, DNA Damage, Embryonic Development genetics, Female, Genes, p53, Genotype, Humans, Male, Mice, Mice, Inbred C57BL genetics, Mice, Knockout, Pregnancy, Telomere genetics, Telomere-Binding Proteins metabolism, Tumor Suppressor Protein p53 metabolism, Abnormalities, Radiation-Induced, Chromosomal Instability radiation effects, Embryonic Development radiation effects, Telomere radiation effects, Tumor Suppressor Protein p53 deficiency
- Abstract
The natural ends of linear chromosomes, the telomeres, recruit specific proteins in the formation of protective caps that preserve the integrity of the genome. Unprotected chromosomes induce DNA damage checkpoint cascades and ultimately lead to senescence both in mouse and man in a p53 dependent manner and initial telomere length setting therefore determines the proliferative capacity of each cell. Yet, only little information is available on telomere biology during embryonic development. We have previously shown that the p53 gene plays a crucial role in the development of malformations (exencephaly, gastroschisis, polydactyly, cleft palate and dwarfism) in control and irradiated mouse embryos. Here, we investigated telomere biology and the outcome of radiation exposure in wild type (p53+/+) and p53-mutant (p53+/-- and--/--) C57BL mouse foetuses irradiated at three different developmental stages. We show that telomeres are significantly shorter in malformed foetuses as compared to normal counterparts. In addition, our results indicate that the observed telomere attrition is primarily associated with p53-deficiency but is also modulated by irradiation, more specifically during the gastrulation and organogenesis stages. In conclusion, we formulate a hypothesis in which telomere shortening is linked to the absence of p53 in mouse foetuses and that when, in the presence of shorter telomeres, these foetuses are irradiated, the chance for the occurrence of developmental defects increases substantially.
- Published
- 2005
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26. Comparison of different protocols for telomere length estimation by combination of quantitative fluorescence in situ hybridization (Q-FISH) and flow cytometry in human cancer cell lines.
- Author
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Derradji H, Bekaert S, Van Oostveldt P, and Baatout S
- Subjects
- Blotting, Southern, Cell Cycle physiology, Cell Line, Tumor, Fixatives, Flow Cytometry, Humans, In Situ Hybridization, Fluorescence, K562 Cells, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Multiple Myeloma pathology, Multiple Myeloma ultrastructure, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Multiple Myeloma genetics, Telomere ultrastructure
- Abstract
Background: The end of eukaryotic chromosomes terminates with nucleoprotein structures called telomeres. They insure several functions including capping the end of the chromosomes, ensuring their stability and protecting them from end-to-end fusion and preventing the activation of the DNA damage checkpoints., Materials and Methods: A flow-FISH methodology, i.e. quantitative fluorescence in situ hybridization (Q-FISH) in combination with flow cytometry, has been developed in our laboratory in order to estimate telomere length in three human cancer cell lines: K-562 (chronic myelogenous leukaemia), IM-9 (multiple myeloma) and 1301 (T cell lymphoblastic leukaemia). Telomeres were visualised after hybridisation with FITC-labelled PNA (Peptide Nucleic Acid) probes. We evaluated the most critical steps of the flow-FISH protocol to ensure reproducibility. Different methodological set ups were compared. Three fixation procedures (ethanol 80%, methanol 80% and formaldehyde 4%) were tested besides different fixation times (15 min and 60 min) as well as hybridization times (2 h and overnight). For each of these protocols the following parameters were compared: forward scatter (related to the cell size), side scatter (related to the cell granularity), DNA (FL3 and FL4 fluorescence) and PNA content (FL1 fluorescence) using an EPICS XL flow cytometer., Results: Regarding the fixation procedures, methanol proved to be the best, followed by ethanol and formaldehyde, with respect to the efficiency to measure the different parameters cited above. Indeed, fixation using methanol gave the optimal PNA signal compared to using ethanol and formaldehyde in two of the studied cell lines (K-562 and 1301); the difference observed was highly significant in the 1301 cell line. The duration of fixation did not show significant interference in the reproducibility of the results for the three cell lines studied. An overnight hybridization appeared to be more effective when compared to the 2-h hybridization in the case of the K-562 cell line., Conclusion: The most important steps of the flow-FISH technique, namely the fixative procedure, as well as the hybridization and the fixation times, were investigated. Considering the latter, suitable protocols were set up for routine and fast telomere length estimation in the cancer cell lines.
- Published
- 2005
27. Increased radiation sensitivity of an eosinophilic cell line following treatment with epigallocatechin-gallate, resveratrol and curcuma.
- Author
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Baatout S, Derradji H, Jacquet P, and Mergeay M
- Subjects
- Annexin A5 pharmacology, Apoptosis, Cell Line, Tumor, Cell Membrane metabolism, Cell Proliferation, Dose-Response Relationship, Drug, Dose-Response Relationship, Radiation, Flow Cytometry, Humans, Necrosis, Radiation Tolerance, Radiation, Ionizing, Resveratrol, Signal Transduction, Time Factors, X-Rays, Catechin analogs & derivatives, Catechin pharmacology, Curcuma metabolism, Eosinophils radiation effects, Leukemia therapy, Plant Extracts therapeutic use, Stilbenes pharmacology
- Abstract
Ionizing radiation is widely used in radiotherapy, in order to promote an apoptotic response in cancerous cells. Since the need to find new substances that would enhance the radiation-induced apoptosis in cancerous cells is great, we studied the effect of epigallocatechin-gallate (EGCG, a tea component), resveratrol (a wine component) and curcuma on cell proliferation and radiation-induced apoptosis in the human leukaemic cell line, EOL-1, derived from a patient with eosinophilic leukaemia. Cells were X-irradiated with 0, 2, 4, 6 or 8 Gy and cultured in the presence of EGCG, resveratrol or curcuma (concentrations ranging from 0 to 200 microM) for 1, 2 or 3 days of culture. Cell proliferation was measured using trypan blue exclusion. Apoptosis was evaluated using light microscopy (morphology study after May-Grunwald Giemsa staining) and flow cytometry (annexin-V staining). Irradiation alone induced a dose-related reduction in cell proliferation and the appearance of polyploid cells in EOL-1 cells. Additionally, EOL-1 cells underwent a dose-related increase of apoptosis which, from the second day on, was accompanied by a dose-related increase of necrosis. When cells were exposed to EGCG, resveratrol or curcuma alone, a decrease in cell proliferation was observed, beginning from 25 microM EGCG and 50 microM resveratrol and curcuma, while an increase in the percentage of apoptotic cells was noted from 50 microM EGCG, 100 microM resveratrol and curcuma in EOL-1 cells, after only one day of culture. Simultaneous exposure to X-irradiation and, EGCG, resveratrol or curcuma resulted in a synergistic decrease of cell proliferation as well as in a synergistic increase of apoptosis and necrosis. These results suggest that, depending on the concentration, EGCG, resveratrol and curcuma enhance radiation-induced apoptosis in the leukaemic cell line, EOL-1 (EGCG >resveratrol >curcuma). In order to further characterise the radiation-induced apoptosis of this leukaemic cell line, other flow cytometrical analyses are in progress.
- Published
- 2005
28. Telomere biology in mammalian germ cells and during development.
- Author
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Bekaert S, Derradji H, and Baatout S
- Subjects
- Animals, DNA Repair, Humans, Longevity, Meiosis physiology, Neural Tube Defects etiology, Reproduction physiology, Telomerase metabolism, Telomere metabolism, Telomere-Binding Proteins metabolism, Aging physiology, Germ Cells physiology, Mammals embryology, Telomere physiology
- Abstract
The development of an organism is a strictly regulated program in which controlled gene expression guarantees the establishment of a specific phenotype. The chromosome termini or so-called telomeres preserve the integrity of the genome within developing cells. In the germline, during early development, and in highly proliferative organs, human telomeres are balanced between shortening processes with each cell division and elongation by telomerase, but once terminally differentiated or mature the equilibrium is shifted to gradual shortening by repression of the telomerase enzyme. Telomere length is to a large extent genetically determined and the neonatal telomere length equilibrium is, in fact, a matter of evolution. Gradual telomere shortening in normal human somatic cells during consecutive rounds of replication eventually leads to critically short telomeres that induce replicative senescence in vitro and probably in vivo. Hence, a molecular clock is set during development, which determines the replicative potential of cells during extrauterine life. Telomeres might be directly or indirectly implicated in longevity determination in vivo, and information on telomere length setting in utero and beyond should help elucidate presumed causal connections between early growth and aging disorders later in life. Only limited information exists concerning the mechanisms underlying overall telomere length regulation in the germline and during early development, especially in humans. The intent of this review is to focus on recent advances in our understanding of telomere biology in germline cells as well as during development (pre- and postimplantation periods) in an attempt to summarize our knowledge about telomere length determination and its importance for normal development in utero and the occurrence of the aging and abnormal phenotype later on.
- Published
- 2004
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29. Study of the combined effect of X-irradiation and epigallocatechin-gallate (a tea component) on the growth inhibition and induction of apoptosis in human cancer cell lines.
- Author
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Baatout S, Jacquet P, Derradji H, Ooms D, Michaux A, and Mergeay M
- Subjects
- Cell Cycle drug effects, Cell Cycle radiation effects, Cell Division drug effects, Cell Division radiation effects, Cell Line, Tumor, HeLa Cells, Humans, K562 Cells, Multiple Myeloma, X-Rays, Anticarcinogenic Agents pharmacology, Apoptosis drug effects, Apoptosis radiation effects, Catechin analogs & derivatives, Catechin pharmacology, Cell Survival drug effects, Cell Survival radiation effects
- Abstract
Over the past 15 years, some potential anticarcinogenic and anti-inflammatory effects of antioxidants have been defined. Antioxidants are known to act as powerful free-radical scavengers. Free radicals are able to induce DNA strand breaks and oxidative modifications of DNA bases and are not only produced naturally in the cell following a stress or respiration but also following ionizing radiation. The present study was undertaken in order to explore whether some antioxidants naturally present in the food or in the beverages could enhance apoptosis in cancerous cells submitted to X-irradiation. Epigallocatechin gallate (EGCG), a potent antioxidant present in tea was tested on three human cancerous cell lines: HeLa (derived from cervix carcinoma), K-562 (derived from chronic myelogenous leukaemia) and IM-9 (derived from multiple myeloma). The parameters investigated were cell proliferation, morphological changes, cell cycle effects and apoptosis. When given alone, irradiation induced a decrease of cell proliferation and an increase of apoptosis as well as the appearance of polyploid cells in the three cell lines. All these effects were dose-dependent. Taking into account the various parameters, IM-9 cells appeared as the most radiation sensitive and HeLa cells as the least radiation sensitive, while K-562 cells exhibited an intermediary radiation sensitivity. EGCG had no effect on cell proliferation, while it induced a dose-dependent increase of apoptosis in the three cell lines. IM-9 cells were again most sensitive to this effect, while HeLa and K-562 cells were slightly less sensitive. A combined treatment by X-irradiation and EGCG resulted in a significant enhancement of apoptosis correlated with a decrease of proliferation in IM-9 and K-562 cells and at a lesser extent, in HeLa cells, compared to treatments by either EGCG or ionising radiation alone. In conclusion, these preliminary results show that depending on the concentration and on the cell line, EGCG could act as a radiation enhancer on cancerous cell lines.
- Published
- 2004
30. Enhanced radiation-induced apoptosis of cancer cell lines after treatment with resveratrol.
- Author
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Baatout S, Derradji H, Jacquet P, Ooms D, Michaux A, and Mergeay M
- Subjects
- Apoptosis drug effects, Apoptosis radiation effects, Cell Division radiation effects, Cell Survival radiation effects, Dose-Response Relationship, Radiation, Female, HeLa Cells, Humans, Radiation Tolerance drug effects, Resveratrol, Tumor Cells, Cultured, Apoptosis physiology, Cell Division drug effects, Cell Survival drug effects, Radiation Tolerance physiology, Stilbenes pharmacology
- Abstract
A search for new agents that can sensitise cancer cells to ionising radiation is of continual interest and mainly due to the use of radiation in cancer therapy. Resveratrol, a powerful antioxidant has been shown to inhibit carcinogenesis in animal models. The purpose of this study was to examine whether resveratrol can sensitise cancer cells to X-irradiation. The human cancer cell lines examined were HELA (cervix carcinoma), K-562 (chronic myeloid leukemia) and IM-9 (multiple myeloma). The assays that were performed following X-irradiation (doses from 0 to 8 Gy) and/or incubation in the presence of resveratrol (concentrations ranging from 0 to 200 microM), were the following: trypan blue exclusion test to determine cell viability, cell morphology after May-Grunwald Giemsa staining, DNA profile analysis by flow cytometry to assess cell cycle distribution and the presence of the sub-G1 peak. The cell lines showed different radiation sensitivity (IM-9, high radiation sensitivity, K-562, intermediate radiation sensitivity and HELA, low radiation sensitivity) as seen by the X-irradiation dose related inhibition of cell growth and induction of apoptosis. The addition of resveratrol alone to the cell cultures induced apoptosis and inhibited cell growth from 50 (IM-9), 100 (EOL-1) or 200 microM (HELA) resveratrol concentrations. Concomitant treatment of the cells with either resveratrol and X-irradiation induced a synergical effect at the highest dose of 200 microM. These results show that resveratrol can act as a potential radiation sensitiser at high concentrations. Further studies need to address the toxicity of resveratrol on normal cells.
- Published
- 2004
31. Cytometric methods to analyze radiation effects.
- Author
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Baatout S and Derradji H
- Subjects
- Animals, Apoptosis radiation effects, Cell Cycle radiation effects, Chromosome Aberrations radiation effects, Comet Assay, Cytophotometry, DNA radiation effects, Flow Cytometry, Humans, In Situ Hybridization, Fluorescence, Micronucleus Tests, Cytological Techniques methods, Eukaryotic Cells radiation effects
- Abstract
Here, we review the most relevant cytometric methods currently used to analyze ionizing radiation effects. Particular interest has been devoted to the following methods: chromosomal aberrations, micronucleus assay, fluorescence in situ hybridization chromosome painting, comet assay, comet-FISH assay as well as flow cytometry.
- Published
- 2004
32. Effect of curcuma on radiation-induced apoptosis in human cancer cells.
- Author
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Baatout S, Derradji H, Jacquet P, Ooms D, Michaux A, and Mergeay M
- Subjects
- Cell Division, Cell Line, Tumor, Curcuma chemistry, DNA metabolism, Dose-Response Relationship, Drug, Flow Cytometry, G1 Phase, HeLa Cells, Humans, K562 Cells, Polyploidy, X-Rays, Apoptosis, Curcuma metabolism, Neoplasms drug therapy, Plant Extracts therapeutic use
- Abstract
There have been considerable efforts to search for naturally occurring substances for the intervention of carcinogenesis. Many components from dietary or medicinal plants have been identified that possess substantial chemopreventive properties. Curcuma, a yellow pigment from Curcuma longa, exhibits anti-inflammatory, antitumor, and antioxidative properties. Although its precise mode of action has not been elucidated so far, studies have shown that chemopreventive action of curcuma might be due to its ability to induce apoptosis (programmed cell death) in cancer cells. This original study was conducted in order to estimate whether curcuma enhances the radiation sensitivity of cancer cells. For this purpose, curcuma (concentrations ranging from 0 to 200 microM) was applied to human cancer cell cultures (HeLa, K-562 and IM-9) with or without X-irradiation (doses comprised between 0 and 8 Gy). Cell proliferation was monitored by trypan blue exclusion. For the estimation of apoptosis, changes in cell morphology and flow cytometry analysis (DNA content and presence of the sub-G1 peak) were performed. Microscopic examination of the curcuma-treated cells (with concentrations above 100 microM) showed a characteristic morphology of apoptosis. Furthermore, cells treated with curcuma exhibited a sub-G1 peak from which the magnitude was proportional to the concentration of curcuma. X-irradiation alone induced polyploidisation and apoptosis of the three cell lines, proportional to the doses of irradiation with a marked difference in radiation sensitivity between the cell lines (IM-9 < K-562 < HELA). However, when radiation and curcuma were applied together, our results showed that in HELA, K-562 and IM-9, curcuma showed a radiation sensitising effect only at the dose of 200 micro M. This result may open a perspective of synergical therapy at the condition to also address the intrinsic toxicity of curcuma on normal cells.
- Published
- 2004
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33. Apoptosis: a mechanism of cell suicide.
- Author
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Derradji H and Baatout S
- Subjects
- Animals, Caspases physiology, Humans, Proto-Oncogene Proteins c-bcl-2 physiology, Apoptosis physiology
- Abstract
In this paper, a general overview on apoptosis (or programmed cell death) is given together with a brief description of the major features characterizing apoptotic cells. Then the most important pathways of apoptosis are described. Thereafter the roles of caspases and the Bcl-2 family members on apoptosis are explained.
- Published
- 2003
34. [Mechanisms of radio-induced apoptosis].
- Author
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Baatout S, Derradji H, Petitfour O, von Suchodoletz H, and Mergeay M
- Subjects
- Animals, Humans, Radiotherapy, Signal Transduction radiation effects, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 radiation effects, Apoptosis radiation effects
- Abstract
A general overview of the activation mechanisms of programmed cell death or apoptosis following an irradiation is given in this review. First, are summarized the main induction pathways of radiation-induced apoptosis by which extracellular (tumor necrosis factor (TNF), Fas ligand, TNF-related apoptosis-inducing ligand (TRAIL)) and intracellular (mitochondria and caspases) signals are integrated. A second part is then devoted to the importance of p53 and of its regulators (ATR, ATM, DNA-PKcs) in the process of radiation-induced apoptosis. Thereafter, signal transduction pathways and more specially the role of some protein kinases (MEKK, SAPK/JNK, p38-MAPK) is treated. At last, a chapter concerns the clinical interest of radiation-induced apoptosis and the implication of apoptosis in the treatment of certain diseases.
- Published
- 2002
- Full Text
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35. Developmental abnormalities induced by X-irradiation in p53 deficient mice.
- Author
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Baatout S, Jacquet P, Michaux A, Buset J, Vankerkom J, Derradji H, Yan J, von Suchodoletz H, de Saint-Georges L, Desaintes C, and Mergeay M
- Subjects
- Animals, Dose-Response Relationship, Radiation, Embryonic and Fetal Development genetics, Female, Fertility drug effects, Fetal Death, Fetal Weight genetics, Fetal Weight radiation effects, Heterozygote, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Pregnancy, Sex Factors, Tumor Suppressor Protein p53 deficiency, Tumor Suppressor Protein p53 metabolism, Abnormalities, Radiation-Induced, Embryonic and Fetal Development radiation effects, Genes, p53 genetics
- Abstract
In order to assess the influence of p53 inactivation on radiation-induced developmental effects, male mice heterozygous for the wild-type p53 allele (mimicking the human Li-Fraumeni syndrome) were crossed with C57BL females, and their heterozygous p53+/- progeny were mated with each other to obtain p53+/-, p53-/- and p53+/+ embryos. Pregnant females were X-irradiated with 0.5 Gy on days 1 (pre-implantation period), 8 or 11 (organogenesis period) of gestation. Dissection of the pregnant females occurred on day 19 of gestation. The p53 genotype of the foetuses was determined by PCR from small pieces of soft tissues. Exencephaly was the only external malformation found in the control group. It affected essentially p53-/- female foetuses. A number of p53+/- and p53+/- control foetuses also showed dwarfism, or underdevelopment. In the group irradiated on day 1, the frequency of abnormal foetuses was, paradoxically, lower than that found in the control group. As in that group, exencephaly and dwarfism constituted the only anomalies that were found. Exencephaly affected only homozygous p53-/- females, while dwarfism concerned either p53-/- or p53+/- foetuses, with a majority of females. Irradiation on day 8 of gestation induced a significant increase in the frequency of abnormal foetuses, compared to the control group. Various malformations were observed in addition to exencephaly, including gastroschisis, polydactyly, cephalic oedema and cleft palate. All malformed foetuses were either homozygous p53-/- or heterozygous p53+/- while most affected foetuses were females, as was the case for dwarf individuals. Irradiation on day 11 did not cause an increase in the frequency of abnormal foetuses, in comparison with the controls. However, a large spectrum of external malformations was again noticed, as in the group irradiated on day 8. All affected foetuses were homozygous p53-/- and there were slightly more abnormal females than males (3 out of 5). No dwarfs were found in this group. Overall, these results confirm the importance of the p53 tumour-suppressor protein for normal embryonic development. They clearly show that homozygous p53-/- (or heterozygous p53+/- to a lesser extent) foetuses are more at risk for radiation-induction of external malformations during the organogenesis period, and that the risk of developing such malformations is much higher for females than for males. In contrast to results published very recently by others, we found that malformed foetuses resulting from an X-irradiation with a low-dose during the highly sensitive period of gastrulation are able to survive to birth.
- Published
- 2002
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