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

Authors:
Dr. Neetu Singh, Ph.D.
Dr. Neetu Singh, Ph.D.
King George's Medical University
Lucknow, Uttar Pradesh | India
Dr. Zhenbang Chen, Ph.D.
Dr. Zhenbang Chen, Ph.D.
Meharry Medical College
Associate Professor
PTEN-AKT, Prostate Cancer
Nashville, TN | United States
Dr. Luoping Zhang, PhD
Dr. Luoping Zhang, PhD
School of Public Health, University of California, Berkeley
Professor
Berkeley, CA | United States
Dr Rabeah Al-Temaimi
Dr Rabeah Al-Temaimi
Faculty of Medicine, Kuwait University
Assistant Professor
Genetics, cell biology, mitochondria
Kuwait
Edward Ratovitski
Edward Ratovitski
The Johns Hopkins University School of Medicine
United States
Professor Fahd Al-Mulla, MD, PhD, PCTM, FRCP
Professor Fahd Al-Mulla, MD, PhD, PCTM, FRCP
Kuwait University/Genatak
Director
Genomic Medicine
Kuwait, Mirqab | Kuwait
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 R 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 Clement Yedjou Colleen S Curran Dale W Laird Daniel C Koch Danielle J Carlin Dean W Felsher Debasish Roy Dustin G Brown Elizabeth P Ryan Emanuela Corsini Emilio Rojas Eun-Yi Moon Ezio Laconi Fabio Marongiu Ferdinando Chiaradonna Firouz Darroudi Francis L Martin Frederik J Van Schooten Gary S Goldberg Gerard Wagemaker Gladys N Nangami Gloria M Calaf Graeme Williams Gregory T Wolf Gudrun Koppen Gunnar Brunborg H Kim Lyerly Harini Krishnan Hasiah Ab Hamid Hemad Yasaei Hideko Sone Hiroshi Kondoh Hosni K 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 A Christopher Josiah Ochieng Juan Fernando Martinez-Leal Judith Weisz Julia Kravchenko Jun Sun Kalan R Prudhomme Kannan Badri Narayanan Karine A Cohen-Solal Kim Moorwood Laetitia Gonzalez Laura Soucek Le Jian Leandro S D'Abronzo Liang-Tzung Lin Lin Li Linda Gulliver Lisa J McCawley Lorenzo Memeo Louis Vermeulen Luc Leyns Mahara Valverde Mahin Khatami Maria Fiammetta Romano Marion Chapellier Marc A Williams Mark Wade Masoud H Manjili Matilde E Lleonart Menghang Xia Michael J Gonzalez Michalis V Karamouzis Micheline Kirsch-Volders Monica Vaccari Nancy B Kuemmerle Nichola Cruickshanks Nicole Kleinstreuer Nik van Larebeke Nuzhat Ahmed Olugbemiga Ogunkua P K Krishnakumar Pankaj Vadgama Paola A Marignani Paramita M Ghosh Patricia Ostrosky-Wegman Patricia A Thompson Paul Dent Petr Heneberg Philippa Darbre Po Sing Leung Pratima Nangia-Makker Qiang Shawn Cheng R Brooks Robey Rabindra Roy Rafaela Andrade-Vieira Ranjeet K 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 Sandra S Wise Sarah N 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 Thomas Sanderson Tiziana Guarnieri Tove Hultman Valérian Dormoy Valerie Odero-Marah Venkata Sabbisetti Veronique Maguer-Satta W Kimryn Rathmell Wilhelm Engström William K Decker William H Bisson Yon Rojanasakul Yunus Luqmani Zhiwei Hu

Carcinogenesis 2015 Jun;36 Suppl 1:S254-96

Department of Surgery, The Ohio State University College of Medicine, The James Comprehensive Cancer Center, Columbus, OH 43210, USA.

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.

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June 2015
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References

(Supplied by CrossRef)
World cancer report 2014
2014
Reducing environmental cancer risk: what we can do now
Reuben et al.

2009

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