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

作者：William H. Goodson, Leroy J. 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 Richard Collins, Andrew Ward, Anna C. Salzberg, Annamaria Colacci, Ann-Karin Hardie Olsen, Arthur S Berg, Barry J. Barclay, Binhua Peter Zhou, Carmen Blanco‐Aparicio, Carolyn J. Baglole, Chenfang Dong, Chiara Mondello, Chia-Wen Hsu, Christian C. G. Naus, Clément G. Yedjou, Colleen S. Curran, Dale W. Laird, Daniel C. Koch, Danielle J. Carlin, Dean W. Felsher, Debasish K. Roy, Dustin G. Brown, Edward A. Ratovitski, Elizabeth P. Ryan, Emanuela Corsini, Emilio R. Rojas, Eun‐Yi Moon, Ezio Laconi, Fabio Marongiu, Fahd Al‐Mulla, Ferdinando Chiaradonna, F. Darroudi, Francis M 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, Herbert Kim Lyerly, Harini Krishnan, Hasiah Ab Hamid, Hemad Yasaei, Hideko Sone, Hiroshi Kondoh, Hosni Khairy Salem, Hsue‐Yin Hsu, Hyun Ho Park, Igor Koturbash, Isabelle Racine Miousse, Anna Ivana Scovassi, James E. Klaunig, Jan Vondráček, Jayadev Raju, Jesse Roman, John Pierce Wise, Jonathan Richard Whitfield, Jordan Woodrick, Joseph Christopher, Josiah Ochieng, Juan Fernando Martínez-Leal, Judith Weisz, Julia S. 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 Adrian Williams, Mark R. Wade, Masoud H. Manjili, Matilde Esther LLeonart, Menghang Xia, Michael J. Guzman, Michalis V. Karamouzis, Micheline Kirsch‐Volders, Monica Vaccari, Nancy B. Kuemmerle, Neetu Singh, Nichola A. Cruickshanks, Nicole Kleinstreuer, Nicolas Van Larebeke, Nuzhat Ahmed, Olugbemiga Ogunkua, P K Krishnakumar, Pankaj M. 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 Abbas Al-Temaimi, Rabindra N. Roy, Rafaela Andrade-Vieira, Ranjeet Kumar Sinha, Rekha S. Mehta, Renza Vento, Riccardo Di Fiore, Richard Ponce‐Cusi, Rita Dornetshuber-Fleiss, Rita Nahta, Robert Craig Castellino, Roberta Palorini, Roslida Abd Hamid, Sabine A. S. Langie, Sakina E. Eltom, Samira A. Brooks, Sandra W. Ryeom, Sandra S. Wise, Sarah Bay, Shelley Anne Harris, Silvana M. 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 S. Sabbisetti, Véronique Maguer‐Satta, W. Kimryn Rathmell, Wilhelm Engström, William Karl Decker, William H. Bisson, Yon Rojanasakul, Yunus A. Luqmani, Zhenbang Chen, Zhiwei Hu · 发表于：Carcinogenesis · 年份：2015 · DOI：10.1093/carcin/bgv039 · 被引用次数：323 · 研究领域：Carcinogens and Genotoxicity Assessment、Effects and risks of endocrine disrupting chemicals、Toxic Organic Pollutants Impact

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 furt...