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

2015; Oxford University Press; Volume: 36; Issue: Suppl 1 Linguagem: Inglês

10.1093/carcin/bgv039

1460-2180

William H. Goodson, Leroy Lowe, David O. Carpenter, Michael Gilbertson, Abdul Manaf Ali, Adela Lopez de Cerain Salsamendi, Ahmed Lasfar, Amancio Carnero, Amaya Azqueta, Amedeo Amedei, Amelia K. Charles, Andrew Collins, Andrew Ward, Anna C. Salzberg, Annamaria Colacci, Ann‐Karin Olsen, Arthur Berg, Barry J. Barclay, Binhua P. Zhou, Carmen Blanco‐Aparicio, Carolyn J. Baglole, Chenfang Dong, Chiara Mondello, Chia-Wen Hsu, Christian C. Naus, Clément G. Yedjou, Colleen S. Curran, Dale W. Laird, Daniel C. Koch, Danielle J. Carlin, Dean W. Felsher, Debasish Roy, Dustin G. Brown, Edward A. Ratovitski, Elizabeth P. Ryan, Emanuela Corsini, Emilio Rojas, Eun‐Yi Moon, Ezio Laconi, Fabio Marongiu, Fahd Al‐Mulla, Ferdinando Chiaradonna, F. Darroudi, Francis L. Martin, Frederik‐Jan van Schooten, Gary S. Goldberg, Gerard Wagemaker, Gladys N. Nangami, Gloria M. Calaf, Graeme P. Williams, Gregory T. Wolf, Gudrun Koppen, Gunnar Brunborg, H. Kim Lyerly, Harini Krishnan, Hasiah Ab Hamid, Hemad Yasaei, Hirohito Sone, Hiroshi Kondoh, Hosni Salem, Hsue‐Yin Hsu, Hyun Ho Park, Igor Koturbash, Isabelle R. Miousse, A. Ivana Scovassi, James E. Klaunig, Jan Vondráček, Jayadev Raju, Jesse Roman, John Pierce Wise, Jonathan R. Whitfield, Jordan Woodrick, Joseph Christopher, Josiah Ochieng, Juan Fernando Martínez-Leal, Judith Weisz, Julia Kravchenko, Jun Sun, Kalan R. Prudhomme, Kannan Badri Narayanan, Karine Cohen-Solal, Kim Moorwood, Laetitia Gonzalez, Laura Soucek, Le Jian, Leandro S. D’Abronzo, Liang Lin, Lin Li, Linda Gulliver, Lisa J. McCawley, Lorenzo Memeo, Louis Vermeulen, Luc Leyns, Luoping Zhang, Mahara Valverde, Mahin Khatami, Maria Fiammetta Romano, Marion Chapellier, Marc A. Williams, Mark Wade, Masoud H. Manjili, Matilde E. Lleonart, Menghang Xia, Michael J. Guzman, Michalis V. Karamouzis, Micheline Kirsch‐Volders, Monica Vaccari, Nancy B. Kuemmerle, Neetu Singh, Nichola Cruickshanks, Nicole Kleinstreuer, Nicolas Van Larebeke, Nuzhat Ahmed, Olugbemiga Ogunkua, P K Krishnakumar, Pankaj Vadgama, Paola A. Marignani, P. Ghosh, Patricia Ostrosky‐Wegman, Patricia A. Thompson, Paul Dent, Petr Heneberg, Philippa D. Darbre, Po Sing Leung, Pratima Nangia‐Makker, Qiang Cheng, R. Brooks Robey, Rabeah Al‐Temaimi, Rabindra Roy, Rafaela Andrade-Vieira, Ranjeet Kumar Sinha, Rekha Mehta, Renza Vento, Riccardo Di Fiore, Richard Ponce‐Cusi, Rita Dornetshuber-Fleiss, Rita Nahta, Robert C. Castellino, Roberta Palorini, Roslida Abd Hamid, Sabine A. S. Langie, Sakina E. Eltom, Samira A. Brooks, Sandra Ryeom, J. Wise, Sarah Bay, Shelley A. Harris, Silvana Papagerakis, Simona Romano, Sofia Pavanello, Staffan Eriksson, Stefano Forte, Stephanie C. Casey, Sudjit Luanpitpong, Tae Jin Lee, Takemi Otsuki, Tao Chen, Thierry Massfelder, J. Thomas Sanderson, Tiziana Guarnieri, Tove Hultman, Valérian Dormoy, Valerie Odero‐Marah, Venkata Sabbisetti, Véronique Maguer‐Satta, W. Kimryn Rathmell, Wilhelm Engström, William K. Decker, William H. Bisson, Yon Rojanasakul, Yunus A. Luqmani, Zhenbang Chen, Zhiwei Hu,

Radioactive contamination and transfer

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.