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14. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: The challenge ahead

Author

Goodson, W.H., III Lowe, L. Carpenter, D.O. Gilbertson, M. Ali, A.M. de Cerain Salsamendi, A.L. Lasfar, A. Carnero, A. Azqueta, A. Amedei, A. Charles, A.K. Collins, A.R. Ward, A. Salzberg, A.C. Colacci, A. Olsen, A.-K. Berg, A. Barclay, B.J. Zhou, B.P. Blanco-Aparicio, C. Baglole, C.J. Dong, C. Mondello, C. Hsu, C.-W. Naus, C.C. Yedjou, C. Curran, C.S. Laird, D.W. Koch, D.C. Carlin, D.J. Felsher, D.W. Roy, D. Brown, D.G. Ratovitski, E. Ryan, E.P. Corsini, E. Rojas, E. Moon, E.-Y. Laconi, E. Marongiu, F. Al-Mulla, F. Chiaradonna, F. Darroudi, F. Martin, F.L. Van Schooten, F.J. Goldberg, G.S. Wagemaker, G. Nangami, G. Calaf, G.M. Williams, G. Wolf, G.T. Koppen, G. Brunborg, G. Kim Lyerly, H. Krishnan, H. Hamid, H.A. Yasaei, H. Sone, H. Kondoh, H. Salem, H.K. Hsu, H.-Y. Park, H.H. Koturbash, I. Miousse, I.R. Ivana Scovassi, A. Klaunig, J.E. Vondráček, J. Raju, J. Roman, J. Wise, J.P., Sr. Whitfield, J.R. Woodrick, J. Christopher, J.A. Ochieng, J. Martinez-Leal, J.F. Weisz, J. Kravchenko, J. Sun, J. Prudhomme, K.R. Narayanan, K.B. Cohen-Solal, K.A. Moorwood, K. Gonzalez, L. Soucek, L. Jian, L. D'Abronzo, L.S. Lin, L.-T. Li, L. Gulliver, L. McCawley, L.J. Memeo, L. Vermeulen, L. Leyns, L. Zhang, L. Valverde, M. Khatami, M. Romano, M.F. Chapellier, M. Williams, M.A. Wade, M. Manjili, M.H. Lleonart, M. Xia, M. Gonzalez, M.J. Karamouzis, M.V. Kirsch-Volders, M. Vaccari, M. Kuemmerle, N.B. Singh, N. Cruickshanks, N. Kleinstreuer, N. Van Larebeke, N. Ahmed, N. Ogunkua, O. Krishnakumar, P.K. Vadgama, P. Marignani, P.A. Ghosh, P.M. Ostrosky-Wegman, P. Thompson, P. Dent, P. Heneberg, P. Darbre, P. Leung, P.S. Nangia-Makker, P. Cheng, Q.S. Brooks Robey, R. Al-Temaimi, R. Roy, R. Andrade-Vieira, R. Sinha, R.K. Mehta, R. Vento, R. Di Fiore, R. Ponce-Cusi, R. Dornetshuber-Fleiss, R. Nahta, R. Castellino, R.C. Palorini, R. Hamid, R.A. Langie, S.A.S. Eltom, S. Brooks, S.A. Ryeom, S. Wise, S.S. Bay, S.N. Harris, S.A. Papagerakis, S. Romano, S. Pavanello, S. Eriksson, S. Forte, S. Casey, S.C. Luanpitpong, S. Lee, T.-J. Otsuki, T. Chen, T. Massfelder, T. Sanderson, T. Guarnieri, T. Hultman, T. Dormoy, V. Odero-Marah, V. Sabbisetti, V. Maguer-Satta, V. Kimryn Rathmell, W. Engström, W. Decker, W.K. Bisson, W.H. Rojanasakul, Y. Luqmani, Y. Chen, Z. Hu, Z.

Abstract

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/ mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology. © The Author 2015.

Published
2015

15. O42. Realizing the European Network of Biological Dosimetry ‘RENEB’: Results of 2 intercomparison exercises for the micronucleus assay

Author

Depuydt, J., primary, Baeyens, A., additional, Barnard, S., additional, Beinke, C., additional, Benedek, A., additional, Beukes, P., additional, Buraczewska, I., additional, Darroudi, F., additional, De Sanctis, S., additional, Dominguez, I., additional, Monteiro Gil, O., additional, Hadjidekova, V., additional, Kis, E., additional, Kulka, U., additional, Lista, F., additional, Lumniczky, K., additional, M’kacher, R., additional, Moquet, J., additional, Obreja, D., additional, Oestreicher, U., additional, Pajic, J., additional, Pastor, N., additional, Popova, L., additional, Regalbuto, E., additional, Ricoul, M., additional, Sabatier, L., additional, Slabbert, J.P., additional, Sommer, S., additional, Testa, A., additional, Thierens, H., additional, Wojcik, A., additional, and Vral, A., additional

Published
2016
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16. Realising the European network of biodosimetry : RENEB-status quo

Author

Kulka, U., Ainsbury, L., Atkinson, M., Barnard, S., Smith, R., Barquinero, J. F., Barrios, L., Bassinet, C., Beinke, C., Cucu, A., Darroudi, F., Fattibene, P., Bortolin, E., Della Monaca, S., Gil, O., Gregoire, E., Hadjidekova, V., Haghdoost, Siamak, Hatzi, V., Hempel, W., Herranz, R., Jaworska, A., Lindholm, C., Lumniczky, K., M'kacher, R., Moertl, S., Montoro, A., Moquet, J., Moreno, M., Noditi, M., Ogbazghi, A., Oestreicher, U., Palitti, F., Pantelias, G., Popescu, I., Prieto, M. J., Roch-Lefevre, S., Roessler, U., Romm, H., Rothkamm, K., Sabatier, L., Sebastia, N., Sommer, S., Terzoudi, G., Testa, A., Thierens, H., Trompier, F., Turai, I., Vandevoorde, C., Vaz, P., Voisin, P., Vral, A., Ugletveit, F., Wieser, A., Woda, C., Wojcik, Andrzej, Kulka, U., Ainsbury, L., Atkinson, M., Barnard, S., Smith, R., Barquinero, J. F., Barrios, L., Bassinet, C., Beinke, C., Cucu, A., Darroudi, F., Fattibene, P., Bortolin, E., Della Monaca, S., Gil, O., Gregoire, E., Hadjidekova, V., Haghdoost, Siamak, Hatzi, V., Hempel, W., Herranz, R., Jaworska, A., Lindholm, C., Lumniczky, K., M'kacher, R., Moertl, S., Montoro, A., Moquet, J., Moreno, M., Noditi, M., Ogbazghi, A., Oestreicher, U., Palitti, F., Pantelias, G., Popescu, I., Prieto, M. J., Roch-Lefevre, S., Roessler, U., Romm, H., Rothkamm, K., Sabatier, L., Sebastia, N., Sommer, S., Terzoudi, G., Testa, A., Thierens, H., Trompier, F., Turai, I., Vandevoorde, C., Vaz, P., Voisin, P., Vral, A., Ugletveit, F., Wieser, A., Woda, C., and Wojcik, Andrzej

Abstract

Creating a sustainable network in biological and retrospective dosimetry that involves a large number of experienced laboratories throughout the European Union (EU) will significantly improve the accident and emergency response capabilities in case of a large-scale radiological emergency. A well-organised cooperative action involving EU laboratories will offer the best chance for fast and trustworthy dose assessments that are urgently needed in an emergency situation. To this end, the EC supports the establishment of a European network in biological dosimetry (RENEB). The RENEB project started in January 2012 involving cooperation of 23 organisations from 16 European countries. The purpose of RENEB is to increase the biodosimetry capacities in case of large-scale radiological emergency scenarios. The progress of the project since its inception is presented, comprising the consolidation process of the network with its operational platform, intercomparison exercises, training activities, proceedings in quality assurance and horizon scanning for new methods and partners. Additionally, the benefit of the network for the radiation research community as a whole is addressed.

Published
2015
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17. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Author

Goodson, WH, Lowe, L, Carpenter, DO, Gilbertson, M, Ali, AM, de Cerain Salsamendi, AL, Lasfar, A, Carnero, A, Azqueta, A, Amedei, A, Charles, AK, Collins, AR, Ward, A, Salzberg, AC, Colacci, A, Olsen, A-K, Berg, A, Barclay, BJ, Zhou, BP, Blanco-Aparicio, C, Baglole, CJ, Dong, C, Mondello, C, Hsu, C-W, Naus, CC, Yedjou, C, Curran, CS, Laird, DW, Koch, DC, Carlin, DJ, Felsher, DW, Roy, D, Brown, DG, Ratovitski, E, Ryan, EP, Corsini, E, Rojas, E, Moon, E-Y, Laconi, E, Marongiu, F, Al-Mulla, F, Chiaradonna, F, Darroudi, F, Martin, FL, Van Schooten, FJ, Goldberg, GS, Wagemaker, G, Nangami, G, Calaf, GM, Williams, G, Wolf, GT, Koppen, G, Brunborg, G, Lyerly, HK, Krishnan, H, Ab Hamid, H, Yasaei, H, Sone, H, Kondoh, H, Salem, HK, Hsu, H-Y, Park, HH, Koturbash, I, Miousse, IR, Scovassi, AI, Klaunig, JE, Vondracek, J, Raju, J, Roman, J, Wise, JP, Whitfield, JR, Woodrick, J, Christopher, JA, Ochieng, J, Fernando Martinez-Leal, J, Weisz, J, Kravchenko, J, Sun, J, Prudhomme, KR, Narayanan, KB, Cohen-Solal, KA, Moorwood, K, Gonzalez, L, Soucek, L, Jian, L, D'Abronzo, LS, Lin, L-T, Li, L, Gulliver, L, McCawley, LJ, Memeo, L, Vermeulen, L, Leyns, L, Zhang, L, Valverde, M, Khatami, M, Romano, MF, Chapellier, M, Williams, MA, Wade, M, Manjili, MH, Lleonart, M, Xia, M, Gonzalez, MJ, Karamouzis, MV, Kirsch-Volders, M, Vaccari, M, Kuemmerle, NB, Singh, N, Cruickshanks, N, Kleinstreuer, N, van Larebeke, N, Ahmed, N, Ogunkua, O, Krishnakumar, PK, Vadgama, P, Marignani, PA, Ghosh, PM, Ostrosky-Wegman, P, Thompson, P, Dent, P, Heneberg, P, Darbre, P, Leung, PS, Nangia-Makker, P, Cheng, QS, Robey, RB, Al-Temaimi, R, Roy, R, Andrade-Vieira, R, Sinha, RK, Mehta, R, Vento, R, Di Fiore, R, Ponce-Cusi, R, Dornetshuber-Fleiss, R, Nahta, R, Castellino, RC, Palorini, R, Abd Hamid, R, Langie, SAS, Eltom, S, Brooks, SA, Ryeom, S, Wise, SS, Bay, SN, Harris, SA, Papagerakis, S, Romano, S, Pavanello, S, Eriksson, S, Forte, S, Casey, SC, Luanpitpong, S, Lee, T-J, Otsuki, T, Chen, T, Massfelder, T, Sanderson, T, Guarnieri, T, Hultman, T, Dormoy, V, Odero-Marah, V, Sabbisetti, V, Maguer-Satta, V, Rathmell, WK, Engstrom, W, Decker, WK, Bisson, WH, Rojanasakul, Y, Luqmani, Y, Chen, Z, Hu, Z, Goodson, WH, Lowe, L, Carpenter, DO, Gilbertson, M, Ali, AM, de Cerain Salsamendi, AL, Lasfar, A, Carnero, A, Azqueta, A, Amedei, A, Charles, AK, Collins, AR, Ward, A, Salzberg, AC, Colacci, A, Olsen, A-K, Berg, A, Barclay, BJ, Zhou, BP, Blanco-Aparicio, C, Baglole, CJ, Dong, C, Mondello, C, Hsu, C-W, Naus, CC, Yedjou, C, Curran, CS, Laird, DW, Koch, DC, Carlin, DJ, Felsher, DW, Roy, D, Brown, DG, Ratovitski, E, Ryan, EP, Corsini, E, Rojas, E, Moon, E-Y, Laconi, E, Marongiu, F, Al-Mulla, F, Chiaradonna, F, Darroudi, F, Martin, FL, Van Schooten, FJ, Goldberg, GS, Wagemaker, G, Nangami, G, Calaf, GM, Williams, G, Wolf, GT, Koppen, G, Brunborg, G, Lyerly, HK, Krishnan, H, Ab Hamid, H, Yasaei, H, Sone, H, Kondoh, H, Salem, HK, Hsu, H-Y, Park, HH, Koturbash, I, Miousse, IR, Scovassi, AI, Klaunig, JE, Vondracek, J, Raju, J, Roman, J, Wise, JP, Whitfield, JR, Woodrick, J, Christopher, JA, Ochieng, J, Fernando Martinez-Leal, J, Weisz, J, Kravchenko, J, Sun, J, Prudhomme, KR, Narayanan, KB, Cohen-Solal, KA, Moorwood, K, Gonzalez, L, Soucek, L, Jian, L, D'Abronzo, LS, Lin, L-T, Li, L, Gulliver, L, McCawley, LJ, Memeo, L, Vermeulen, L, Leyns, L, Zhang, L, Valverde, M, Khatami, M, Romano, MF, Chapellier, M, Williams, MA, Wade, M, Manjili, MH, Lleonart, M, Xia, M, Gonzalez, MJ, Karamouzis, MV, Kirsch-Volders, M, Vaccari, M, Kuemmerle, NB, Singh, N, Cruickshanks, N, Kleinstreuer, N, van Larebeke, N, Ahmed, N, Ogunkua, O, Krishnakumar, PK, Vadgama, P, Marignani, PA, Ghosh, PM, Ostrosky-Wegman, P, Thompson, P, Dent, P, Heneberg, P, Darbre, P, Leung, PS, Nangia-Makker, P, Cheng, QS, Robey, RB, Al-Temaimi, R, Roy, R, Andrade-Vieira, R, Sinha, RK, Mehta, R, Vento, R, Di Fiore, R, Ponce-Cusi, R, Dornetshuber-Fleiss, R, Nahta, R, Castellino, RC, Palorini, R, Abd Hamid, R, Langie, SAS, Eltom, S, Brooks, SA, Ryeom, S, Wise, SS, Bay, SN, Harris, SA, Papagerakis, S, Romano, S, Pavanello, S, Eriksson, S, Forte, S, Casey, SC, Luanpitpong, S, Lee, T-J, Otsuki, T, Chen, T, Massfelder, T, Sanderson, T, Guarnieri, T, Hultman, T, Dormoy, V, Odero-Marah, V, Sabbisetti, V, Maguer-Satta, V, Rathmell, WK, Engstrom, W, Decker, WK, Bisson, WH, Rojanasakul, Y, Luqmani, Y, Chen, Z, and Hu, Z

Abstract

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.

Published
2015

18. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: The challenge ahead

Author

Goodson, W, Lowe, L, Carpenter, D, Gilbertson, M, Ali, A, de Cerain Salsamendi, A, Lasfar, A, Carnero, A, Azqueta, A, Amedei, A, Charles, A, Collins, A, Ward, A, Salzberg, A, Colacci, A, Olsen, A, Berg, A, Barclay, B, Zhou, B, Blanco Aparicio, C, Baglole, C, Dong, C, Mondello, C, Hsu, C, Naus, C, Yedjou, C, Curran, C, Laird, D, Koch, D, Carlin, D, Felsher, D, Roy, D, Brown, D, Ratovitski, E, Ryan, E, Corsini, E, Rojas, E, Moon, E, Laconi, E, Marongiu, F, Al Mulla, F, Chiaradonna, F, Darroudi, F, Martin, F, Van Schooten, F, Goldberg, G, Wagemaker, G, Nangami, G, Calaf, G, Williams, G, Wolf, G, Koppen, G, Brunborg, G, Kim Lyerly, H, Krishnan, H, Hamid, H, Yasaei, H, Sone, H, Kondoh, H, Salem, H, Hsu, H, Park, H, Koturbash, I, Miousse, I, Ivana Scovassi, A, Klaunig, J, Vondráček, J, Raju, J, Roman, J, Wise, J, Whitfield, J, Woodrick, J, Christopher, J, Ochieng, J, Martinez Leal, J, Weisz, J, Kravchenko, J, Sun, J, Prudhomme, K, Narayanan, K, Cohen Solal, K, Moorwood, K, Gonzalez, L, Soucek, L, Jian, L, D'Abronzo, L, Lin, L, Li, L, Gulliver, L, Mccawley, L, Memeo, L, Vermeulen, L, Leyns, L, Zhang, L, Valverde, M, Khatami, M, Romano, M, Chapellier, M, Williams, M, Wade, M, Manjili, M, Lleonart, M, Xia, M, Gonzalez, M, Karamouzis, M, Kirsch Volders, M, Vaccari, M, Kuemmerle, N, Singh, N, Cruickshanks, N, Kleinstreuer, N, Van Larebeke, N, Ahmed, N, Ogunkua, O, Krishnakumar, P, Vadgama, P, Marignani, P, Ghosh, P, Ostrosky Wegman, P, Thompson, P, Dent, P, Heneberg, P, Darbre, P, Leung, P, Nangia Makker, P, Cheng, Q, Brooks Robey, R, Al Temaimi, R, Roy, R, Andrade Vieira, R, Sinha, R, Mehta, R, Vento, R, Di Fiore, R, Ponce Cusi, R, Dornetshuber Fleiss, R, Nahta, R, Castellino, R, Palorini, R, Hamid, R, Langie, S, Eltom, S, Brooks, S, Ryeom, S, Wise, S, Bay, S, Harris, S, Papagerakis, S, Romano, S, Pavanello, S, Eriksson, S, Forte, S, Casey, S, Luanpitpong, S, Lee, T, Otsuki, T, Chen, T, Massfelder, T, Sanderson, T, Guarnieri, T, Hultman, T, Dormoy, V, Odero Marah, V, Sabbisetti, V, Maguer Satta, V, Kimryn Rathmell, W, Engström, W, Decker, W, Bisson, W, Rojanasakul, Y, Luqmani, Y, Chen, Z, Hu, Z, CHIARADONNA, FERDINANDO, PALORINI, ROBERTA, Hu, Z., Goodson, W, Lowe, L, Carpenter, D, Gilbertson, M, Ali, A, de Cerain Salsamendi, A, Lasfar, A, Carnero, A, Azqueta, A, Amedei, A, Charles, A, Collins, A, Ward, A, Salzberg, A, Colacci, A, Olsen, A, Berg, A, Barclay, B, Zhou, B, Blanco Aparicio, C, Baglole, C, Dong, C, Mondello, C, Hsu, C, Naus, C, Yedjou, C, Curran, C, Laird, D, Koch, D, Carlin, D, Felsher, D, Roy, D, Brown, D, Ratovitski, E, Ryan, E, Corsini, E, Rojas, E, Moon, E, Laconi, E, Marongiu, F, Al Mulla, F, Chiaradonna, F, Darroudi, F, Martin, F, Van Schooten, F, Goldberg, G, Wagemaker, G, Nangami, G, Calaf, G, Williams, G, Wolf, G, Koppen, G, Brunborg, G, Kim Lyerly, H, Krishnan, H, Hamid, H, Yasaei, H, Sone, H, Kondoh, H, Salem, H, Hsu, H, Park, H, Koturbash, I, Miousse, I, Ivana Scovassi, A, Klaunig, J, Vondráček, J, Raju, J, Roman, J, Wise, J, Whitfield, J, Woodrick, J, Christopher, J, Ochieng, J, Martinez Leal, J, Weisz, J, Kravchenko, J, Sun, J, Prudhomme, K, Narayanan, K, Cohen Solal, K, Moorwood, K, Gonzalez, L, Soucek, L, Jian, L, D'Abronzo, L, Lin, L, Li, L, Gulliver, L, Mccawley, L, Memeo, L, Vermeulen, L, Leyns, L, Zhang, L, Valverde, M, Khatami, M, Romano, M, Chapellier, M, Williams, M, Wade, M, Manjili, M, Lleonart, M, Xia, M, Gonzalez, M, Karamouzis, M, Kirsch Volders, M, Vaccari, M, Kuemmerle, N, Singh, N, Cruickshanks, N, Kleinstreuer, N, Van Larebeke, N, Ahmed, N, Ogunkua, O, Krishnakumar, P, Vadgama, P, Marignani, P, Ghosh, P, Ostrosky Wegman, P, Thompson, P, Dent, P, Heneberg, P, Darbre, P, Leung, P, Nangia Makker, P, Cheng, Q, Brooks Robey, R, Al Temaimi, R, Roy, R, Andrade Vieira, R, Sinha, R, Mehta, R, Vento, R, Di Fiore, R, Ponce Cusi, R, Dornetshuber Fleiss, R, Nahta, R, Castellino, R, Palorini, R, Hamid, R, Langie, S, Eltom, S, Brooks, S, Ryeom, S, Wise, S, Bay, S, Harris, S, Papagerakis, S, Romano, S, Pavanello, S, Eriksson, S, Forte, S, Casey, S, Luanpitpong, S, Lee, T, Otsuki, T, Chen, T, Massfelder, T, Sanderson, T, Guarnieri, T, Hultman, T, Dormoy, V, Odero Marah, V, Sabbisetti, V, Maguer Satta, V, Kimryn Rathmell, W, Engström, W, Decker, W, Bisson, W, Rojanasakul, Y, Luqmani, Y, Chen, Z, Hu, Z, CHIARADONNA, FERDINANDO, PALORINI, ROBERTA, and Hu, Z.

Abstract

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/ mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.

Published
2015

19. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: The challenge ahead

Author

Goodson, W., Lowe, L., Carpenter, D., Gilbertson, M., Ali, A., de Cerain Salsamendi, A., Lasfar, A., Carnero, A., Azqueta, A., Amedei, A., Charles, A., Collins, A., Ward, A., Salzberg, A., Colacci, A., Olsen, A., Berg, A., Barclay, B., Zhou, B., Blanco-Aparicio, C., Baglole, C., Dong, C., Mondello, C., Hsu, C., Naus, C., Yedjou, C., Curran, C., Laird, D., Koch, D., Carlin, D., Felsher, D., Roy, D., Brown, D., Ratovitski, E., Ryan, E., Corsini, E., Rojas, E., Moon, E., Laconi, E., Marongiu, F., Al-Mulla, F., Chiaradonna, F., Darroudi, F., Martin, F., Van Schooten, F., Goldberg, G., Wagemaker, G., Nangami, G., Calaf, G., Williams, G., Wolf, G., Koppen, G., Brunborg, G., Kim Lyerly, H., Krishnan, H., Hamid, H., Yasaei, H., Sone, H., Kondoh, H., Salem, H., Hsu, H., Park, H., Koturbash, I., Miousse, I., Ivana Scovassi, A., Klaunig, J., Vondrácek, J., Raju, J., Roman, J., Wise, J., Whitfield, J., Woodrick, J., Christopher, J., Ochieng, J., Martinez-Leal, J., Weisz, J., Kravchenko, J., Sun, J., Prudhomme, K., Narayanan, K., Cohen-Solal, K., Moorwood, K., Gonzalez, L., Soucek, L., Jian, Le, D'Abronzo, L., Lin, L., Li, L., Gulliver, L., McCawley, L., Memeo, L., Vermeulen, L., Leyns, L., Zhang, L., Goodson, W., Lowe, L., Carpenter, D., Gilbertson, M., Ali, A., de Cerain Salsamendi, A., Lasfar, A., Carnero, A., Azqueta, A., Amedei, A., Charles, A., Collins, A., Ward, A., Salzberg, A., Colacci, A., Olsen, A., Berg, A., Barclay, B., Zhou, B., Blanco-Aparicio, C., Baglole, C., Dong, C., Mondello, C., Hsu, C., Naus, C., Yedjou, C., Curran, C., Laird, D., Koch, D., Carlin, D., Felsher, D., Roy, D., Brown, D., Ratovitski, E., Ryan, E., Corsini, E., Rojas, E., Moon, E., Laconi, E., Marongiu, F., Al-Mulla, F., Chiaradonna, F., Darroudi, F., Martin, F., Van Schooten, F., Goldberg, G., Wagemaker, G., Nangami, G., Calaf, G., Williams, G., Wolf, G., Koppen, G., Brunborg, G., Kim Lyerly, H., Krishnan, H., Hamid, H., Yasaei, H., Sone, H., Kondoh, H., Salem, H., Hsu, H., Park, H., Koturbash, I., Miousse, I., Ivana Scovassi, A., Klaunig, J., Vondrácek, J., Raju, J., Roman, J., Wise, J., Whitfield, J., Woodrick, J., Christopher, J., Ochieng, J., Martinez-Leal, J., Weisz, J., Kravchenko, J., Sun, J., Prudhomme, K., Narayanan, K., Cohen-Solal, K., Moorwood, K., Gonzalez, L., Soucek, L., Jian, Le, D'Abronzo, L., Lin, L., Li, L., Gulliver, L., McCawley, L., Memeo, L., Vermeulen, L., Leyns, L., and Zhang, L.

Abstract

© The Author 2015. Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/ mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.

Published
2015

21. PCC and COBRA-FISH a new tool to characterize primary cervical carcinomas: To assess hall-marks and stage specificity

Author

Darroudi, F., Bergs, J.W.J., Bezrookove, V., Buist, M.R., Stalpers, L.J., and Franken, N.A.P.

Subjects
Chemically induced PCC COBRA-FISH Primary cervical cancer Chromosomal abnormalities Stage specificity premature chromosome condensation comparative genomic hybridization in-situ hybridization cancer cell-lines recurrent pattern aberrations lymphocytes tumors instability integration
Abstract

A newly developed assay based on chemically induced premature chromosome condensation (PCC) and multi-color combined binary ratio labeling (COBRA) fluorescence in situ hybridization (FISH) techniques have been implemented in order to investigate for the first time for recurrent cytogenetic aberrations in primary cervical carcinoma (derived directly from biopsies) at different stages of progression. The cytogenetic profiles of 17 biopsies derived from 14 and 3 cervical cancer patients with squamous-cell carcinomas (Sq) and with adenocarcinomas (Ad), respectively, were assessed. Frequencies of both structural as well as numerical aberrations were found to be higher in Sq than in Ad. The analysis revealed that even in early tumors stages (IB1) have a higher frequency of chromosome-losses and -gains as well as chromosomal alterations as compared to normal cells. A positive trend was found between stage advancement of cervical tumors and the frequency of numerical and structural aberrations. No specific and common chromosomal abnormality (e.g. distinct clones of translocation) was found among cervical carcinoma at the different stages (IB1, IIA and IIB). However, a distinct difference was found between stage IIIB and lower tumor stages, as all analyzed IIIB samples revealed a near tetraploid karyotype. Furthermore, all studied metaphases were aberrant and had a high frequency of translocations. PCC-COBRA-FISH characterization of a common type of an established culture from cervical carcinoma CSCC-1 revealed a triploidy/tetraploidy karyotype with several structural aberrations. In general, no similarity was found between this model and early stages of primary tumors. The newly established assay has a novel potential and can reveal the original status of primary tumors at different stages. Crown Copyright (C) 2009 Published by Elsevier Ltd. All rights reserved.

Published
2010

22. Realising the European network of biodosimetry: RENEB--status quo

Author

Kulka, U., primary, Ainsbury, L., additional, Atkinson, M., additional, Barnard, S., additional, Smith, R., additional, Barquinero, J. F., additional, Barrios, L., additional, Bassinet, C., additional, Beinke, C., additional, Cucu, A., additional, Darroudi, F., additional, Fattibene, P., additional, Bortolin, E., additional, Monaca, S. D., additional, Gil, O., additional, Gregoire, E., additional, Hadjidekova, V., additional, Haghdoost, S., additional, Hatzi, V., additional, Hempel, W., additional, Herranz, R., additional, Jaworska, A., additional, Lindholm, C., additional, Lumniczky, K., additional, M'kacher, R., additional, Mortl, S., additional, Montoro, A., additional, Moquet, J., additional, Moreno, M., additional, Noditi, M., additional, Ogbazghi, A., additional, Oestreicher, U., additional, Palitti, F., additional, Pantelias, G., additional, Popescu, I., additional, Prieto, M. J., additional, Roch-Lefevre, S., additional, Roessler, U., additional, Romm, H., additional, Rothkamm, K., additional, Sabatier, L., additional, Sebastia, N., additional, Sommer, S., additional, Terzoudi, G., additional, Testa, A., additional, Thierens, H., additional, Trompier, F., additional, Turai, I., additional, Vandevoorde, C., additional, Vaz, P., additional, Voisin, P., additional, Vral, A., additional, Ugletveit, F., additional, Wieser, A., additional, Woda, C., additional, and Wojcik, A., additional

Published
2014
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27. Realising the European Network of Biodosimetry (RENEB)

Author

Kulka, U., Ainsbury, L., Atkinson, M., Barquinero, J. F., Barrios, L., Beinke, C., Bognar, G., Cucu, A., Darroudi, F., Fattibene, P., Gil, O., Gregoire, E., Hadjidekova, V., Haghdoost, Siamak, Herranz, R., Jaworska, A., Lindholm, C., Mkacher, R., Moertl, S., Montoro, A., Moquet, J., Moreno, M., Ogbazghi, A., Oestreicher, U., Palitti, F., Pantelias, G., Popescu, I., Prieto, M. J., Romm, H., Rothkamm, K., Sabatier, L., Sommer, S., Terzoudi, G., Testa, A., Thierens, H., Trompier, F., Turai, I., Vandersickel, V., Vaz, P., Voisin, P., Vral, A., Ugletveit, F., Woda, C., Wojcik, Andrzej, Kulka, U., Ainsbury, L., Atkinson, M., Barquinero, J. F., Barrios, L., Beinke, C., Bognar, G., Cucu, A., Darroudi, F., Fattibene, P., Gil, O., Gregoire, E., Hadjidekova, V., Haghdoost, Siamak, Herranz, R., Jaworska, A., Lindholm, C., Mkacher, R., Moertl, S., Montoro, A., Moquet, J., Moreno, M., Ogbazghi, A., Oestreicher, U., Palitti, F., Pantelias, G., Popescu, I., Prieto, M. J., Romm, H., Rothkamm, K., Sabatier, L., Sommer, S., Terzoudi, G., Testa, A., Thierens, H., Trompier, F., Turai, I., Vandersickel, V., Vaz, P., Voisin, P., Vral, A., Ugletveit, F., Woda, C., and Wojcik, Andrzej

Abstract

In Europe, a network for biological dosimetry has been created to strengthen the emergency preparedness and response capabilities in case of a large-scale nuclear accident or radiological emergency. Through the RENEB (Realising the European Network of Biodosimetry) project, 23 experienced laboratories from 16 European countries will establish a sustainable network for rapid, comprehensive and standardised biodosimetry provision that would be urgently required in an emergency situation on European ground. The foundation of the network is formed by five main pillars: (1) the ad hoc operational basis, (2) a basis of future developments, (3) an effective quality-management system, (4) arrangements to guarantee long-term sustainability and (5) awareness of the existence of RENEB. RENEB will thus provide a mechanism for quick, efficient and reliable support within the European radiation emergency management. The scientific basis of RENEB will concurrently contribute to increased safety in the field of radiation protection., AuthorCount:44

Published
2012
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28. REVIEW OF RETROSPECTIVE DOSIMETRY TECHNIQUES FOR EXTERNAL IONISING RADIATION EXPOSURES.

Author

Ainsbury, E A, Bakhanova, E, Barquinero, J F, Brai, M, Chumak, V, Correcher, V, Darroudi, F, Fattibene, P, Gruel, G, Guclu, I, Horn, S, Jaworska, A, Kulka, U, Lindholm, C, Lloyd, D, Longo, A, Marrale, M, Monteiro Gil, O, Oestreicher, U, Pajic, J, Rakic, B, Romm, H, Trompier, F, Veronese, I, Voisin, P, Vral, A, Whitehouse, C A, Wieser, A, Woda, C, Wojcik, Andrzej, Rothkamm, K, Ainsbury, E A, Bakhanova, E, Barquinero, J F, Brai, M, Chumak, V, Correcher, V, Darroudi, F, Fattibene, P, Gruel, G, Guclu, I, Horn, S, Jaworska, A, Kulka, U, Lindholm, C, Lloyd, D, Longo, A, Marrale, M, Monteiro Gil, O, Oestreicher, U, Pajic, J, Rakic, B, Romm, H, Trompier, F, Veronese, I, Voisin, P, Vral, A, Whitehouse, C A, Wieser, A, Woda, C, Wojcik, Andrzej, and Rothkamm, K

Abstract

The current focus on networking and mutual assistance in the management of radiation accidents or incidents has demonstrated the importance of a joined-up approach in physical and biological dosimetry. To this end, the European Radiation Dosimetry Working Group 10 on 'Retrospective Dosimetry' has been set up by individuals from a wide range of disciplines across Europe. Here, established and emerging dosimetry methods are reviewed, which can be used immediately and retrospectively following external ionising radiation exposure. Endpoints and assays include dicentrics, translocations, premature chromosome condensation, micronuclei, somatic mutations, gene expression, electron paramagnetic resonance, thermoluminescence, optically stimulated luminescence, neutron activation, haematology, protein biomarkers and analytical dose reconstruction. Individual characteristics of these techniques, their limitations and potential for further development are reviewed, and their usefulness in specific exposure scenarios is discussed. Whilst no single technique fulfils the criteria of an ideal dosemeter, an integrated approach using multiple techniques tailored to the exposure scenario can cover most requirements., authorCount :31

Published
2011
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29. Development of test systems for the detection of compounds that prevent the genotoxic effects of heterocyclic aromatic amines : preliminary results with constituents of cruciferous vegetables and other dietary constituents

Author

Schwab C, Kassie F, Hm, Qin, Sanyal R, Im, Uhl, Hietsch G, Sylvie Rabot, Darroudi F, Knasmüller S, ProdInra, Migration, Unité de recherche d'Écologie et Physiologie du Système Digestif (UEPSD), and Institut National de la Recherche Agronomique (INRA)

Subjects
Carcinoma, Hepatocellular, Plant Extracts, [SDV]Life Sciences [q-bio], Antimutagenic Agents, Chemoprevention, Diet, Rats, [SDV] Life Sciences [q-bio], EFFET PROTECTEUR, ANTICARCINOGENE, Heterocyclic Compounds, Cell Line, Tumor, Vegetables, Animals, Humans, Comet Assay, DNA Damage
Abstract

Over the past decades, strong efforts have been made to identify dietary constituents that protect against the genotoxic effects of heterocyclic aromatic amines (HAAs). However, most of the methods that have been used, in particular in vitro assays that require the addition of exogenous enzyme homogenates, have only a limited predictive value because important protective mechanisms are not adequately represented and may give misleading results. Therefore, we attempted to develop improved test systems, namely assays, with human hepatoma cells and single-cell gel electrophoresis (SCGE) tests with rats. Genotoxicity tests with human derived Hep G2 cells reflect the genotoxic effects of HAAs better than other in vitro systems. They also enable the detection of protective effects since the human derived hepatoma cells possess phase I and phase II enzymes that are involved in the activation/ detoxification of the amines. The most appropriate endpoint for experiments with Hep G2 cells appears to be micronucleus induction, but protocols for other endpoints are available as well. The second promising model is the SCGE ("comet") assay with rats that was used successfully to measure protective effects of constituents of cruciferous vegetables against 2-amino-3-methylimidazo[4,5-flquinoline (IQ) in the liver and in the colon mucosa. The present study describes the experimental design of the new approaches, as well as results obtained with various dietary constituents.

Published
1999

31. Realising the European Network of Biodosimetry (RENEB)

Author

Kulka, U., primary, Ainsbury, L., additional, Atkinson, M., additional, Barquinero, J. F., additional, Barrios, L., additional, Beinke, C., additional, Bognar, G., additional, Cucu, A., additional, Darroudi, F., additional, Fattibene, P., additional, Gil, O., additional, Gregoire, E., additional, Hadjidekova, V., additional, Haghdoost, S., additional, Herranz, R., additional, Jaworska, A., additional, Lindholm, C., additional, Mkacher, R., additional, Mortl, S., additional, Montoro, A., additional, Moquet, J., additional, Moreno, M., additional, Ogbazghi, A., additional, Oestreicher, U., additional, Palitti, F., additional, Pantelias, G., additional, Popescu, I., additional, Prieto, M. J., additional, Romm, H., additional, Rothkamm, K., additional, Sabatier, L., additional, Sommer, S., additional, Terzoudi, G., additional, Testa, A., additional, Thierens, H., additional, Trompier, F., additional, Turai, I., additional, Vandersickel, V., additional, Vaz, P., additional, Voisin, P., additional, Vral, A., additional, Ugletveit, F., additional, Woda, C., additional, and Wojcik, A., additional

Published
2012
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32. Review of retrospective dosimetry techniques for external ionising radiation exposures

Author

Ainsbury, E. A., primary, Bakhanova, E., additional, Barquinero, J. F., additional, Brai, M., additional, Chumak, V., additional, Correcher, V., additional, Darroudi, F., additional, Fattibene, P., additional, Gruel, G., additional, Guclu, I., additional, Horn, S., additional, Jaworska, A., additional, Kulka, U., additional, Lindholm, C., additional, Lloyd, D., additional, Longo, A., additional, Marrale, M., additional, Monteiro Gil, O., additional, Oestreicher, U., additional, Pajic, J., additional, Rakic, B., additional, Romm, H., additional, Trompier, F., additional, Veronese, I., additional, Voisin, P., additional, Vral, A., additional, Whitehouse, C. A., additional, Wieser, A., additional, Woda, C., additional, Wojcik, A., additional, and Rothkamm, K., additional

Published
2010
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36. REALISING THE EUROPEAN NETWORKOF BIODOSIMETRY: RENEB--STATUS QUO.

Author

Kulka, U., Ainsbury, L., Atkinson, M., Barnard, S., Smith, R., Barquinero, J. F., Barrios, L., Bassinet, C., Beinke, C., Cucu, A., Darroudi, F., Fattibene, P., Bortolin, E., Della Monaca, S., Gil, O., Gregoire, E., Hadjidekova, V., Haghdoost, S., Hatzil, V., and Hempel, W.

Subjects
RADIATION dosimetry, LABORATORIES, EMERGENCY management, IONIZING radiation, SCIENTIFIC community
Abstract

Creating a sustainable network in biological and retrospective dosimetry that involves a large number of experienced laboratories throughout the European Union (EU) will significantly improve the accident and emergency response capabilities in case of a large-scale radiological emergency. Awell-organised cooperative action involving EU laboratories will offer the best chance for fast and trustworthy dose assessments that are urgently needed in an emergency situation. To this end, the EC supports the establishment of a European network in biological dosimetry (RENEB). The RENEB project started in January 2012 involving cooperation of 23 organisations from 16 European countries. The purpose of RENEB is to increase the biodosimetry capacities in case of large-scale radiological emergency scenarios. The progress of the project since its inception is presented, comprising the consolidation process of the network with its operational platform, intercomparison exercises, training activities, proceedings in quality assurance and horizon scanning for new methods and partners. Additionally, the benefit of the network for the radiation research community as a whole is addressed. [ABSTRACT FROM AUTHOR]

Published
2015
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38. Review of translocations detected by FISH for retrospective biological dosimetry applications

Author

Edwards, A. A., primary, Lindholm, C., additional, Darroudi, F., additional, Stephan, G., additional, Romm, H., additional, Barquinero, J., additional, Barrios, L., additional, Caballin, M. R., additional, Roy, L., additional, Whitehouse, C. A., additional, Tawn, E. J., additional, Moquet, J., additional, Lloyd, D. C., additional, and Voisin, P., additional

Published
2005
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39. Translocation yields in peripheral blood lymphocytes from control populations

Author

Whitehouse, CA, primary, Edwards, AA, additional, Tawn, EJ, additional, Stephan, G, additional, Oestreicher, U, additional, Moquet, JE, additional, Lloyd, DC, additional, Roy, L, additional, Voisin, P, additional, Lindholm, C, additional, Barquinero, J, additional, Barrios, L, additional, Caballin, MR, additional, Darroudi, F, additional, and Fomina, J, additional

Published
2005
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45. Development and validation of alternative metabolic systems for mutagenicity testing in short-term assays

Author

UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique, Rueff, J., Chiapella, C, Chipman, JK, Darroudi, F, Silva, ID, Duvergervanbogaert, M., Fonti, E, Glatt, HR, Isern, P, Laires, A, Leonard, A., Llagostera, M, Mossesso, P, Natarajan, AT, Palitti, F, Rodrigues, AS, Schinoppi, A, Turchi, G, WerleSchneider, G, UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique, Rueff, J., Chiapella, C, Chipman, JK, Darroudi, F, Silva, ID, Duvergervanbogaert, M., Fonti, E, Glatt, HR, Isern, P, Laires, A, Leonard, A., Llagostera, M, Mossesso, P, Natarajan, AT, Palitti, F, Rodrigues, AS, Schinoppi, A, Turchi, G, and WerleSchneider, G

Abstract

We present here the results obtained within the framework of an EU funded project aimed to develop and validate alternative metabolic activating systems to be used in short-term mutagenicity assays, in order to reduce the use of laboratory animals for toxicology testing. The activating systems studied were established cell lines (Hep G2, CHEL), genetically engineered V79 cell lines expressing specific rat cytochromes P450, erythrocyte-derived systems, CYP-mimetic chemical systems and plant homogenates. The metabolically competent cell lines were used as indicator cells for genotoxic effects as well as for the preparation of external activating systems using other indicator cells. The following endpoints were used: micronuclei, chromosomal aberrations and sister chromatid exchanges, mutations at the hprt locus, gene mutations in bacteria (Ames test), unscheduled DNA synthesis and DNA breaks detected in the comet assay, All metabolic systems employed activated some promutagens. With some of them, promutagens belonging to many different classes of chemicals were activated to genotoxicants, including carcinogens negative in liver S9-mediated assays. In other cases, the use of the new activating systems allowed the detection of mutagens at much lower substrate concentrations than in liver S9-mediated assays. Therefore, the alternative metabolizing systems, which do not require the use of laboratory animals, have a substantial potential in in vitro toxicology, in the basic genotoxicity testing as well as in the elucidation of activation mechanisms. However, since the data basis is much smaller for the new systems than for the activating systems produced from subcellular liver preparations, the overlapping use of both systems is recommended for the present and near future. For example, Liver S9 preparations may be used with some indicator systems (e.g., bacterial mutagenicity), and metabolically competent mammalian cell lines may be used with other indicator systems (e.g.

Published
1996

47. Collaborative exercise on the use of FISH chromosome painting for retrospective biodosimetry of Mayak nuclear-industrial personnel

Author

Bauchinger, M., primary, Braselmann, H., additional, Savage, J. R. K., additional, Natarajan, A. T., additional, Terzoudi, G. I., additional, Pantelias, G. E., additional, Darroudi, F., additional, Figgitt, M., additional, Griffin, C. S., additional, Knehr, S., additional, Okladnikova, N. D., additional, Santos, S., additional, and Snigiryova, G., additional

Published
2001
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