Assessing the Carcinogenic Potential of Low-Dose Exposures to Chemical Mixtures in the Environment: The Challenge Ahead

Authors

William Goodson, California Pacific Medical Center Research Institute
Leroy Lowe, Getting to Know Cancer
David Carpenter, University at Albany, State University of New York
Michael Gilbertson, Getting to Know Cancer
Abdul Manaf Ali, Sultan Zainal Abidin University
Adela Lopez de Cerain Salsamendi Lopez de Cerain Salsamendi, University of Navarra
Ahmed Lasfar, Rutgers University
Amancio Carnero, Universidad de Sevilla
Amaya Azqueta, University of Navarra
Amedeo Amedei, University of Florence
Amelia Charles, University of Reading
Andrew Collins, University of Oslo
Andrew Ward, University of Bath
Anna Salzberg, The Pennsylvania State University
Anna Colacci, Environmental Protection and Health Prevention Agency, Bologna, Italy
Ann-Karin Olsen, Norwegian Institute of Public Health
Arthur Berg, The Pennsylvania State University
Barry Barclay, Planet Biotechnologies Inc., St Albert, Alberta T8N 5K4, Canada
Binhua Zhou, University of Kentucky
Carmen Blanco-Aparicio, Spanish National Cancer Research Centre
Carolyn Baglole, McGill University
Chenfang Dong, University of Kentucky
Chiara Mondello, Istituto di Genetica Molecolare, CNR, Via Abbiategrasso 207, 27100 Pavia, Italy
Chia-Wen Hsu, National Center for Advancing Translational Sciences, National Institutes of Health
Christian Naus, University of British Columbia
Clement Yedjou, Jackson State University
Colleen Curran, University of Wisconsin-Madison
Dale Laird, University of Western OntarioFollow
Daniel Koch, Stanford University
Danielle Carlin, National Institute of Environmental Health Sciences
Dean Felsher, Stanford University
Debasish Roy, City University of New York
Dustin Brown, Colorado State University - Fort Collins
Edward Ratovitski, Johns Hopkins University
Elizabeth Ryan, Colorado State University - Fort Collins
Emanuela Corsini, Università degli Studi di Milano
Emilio Rojas, National Autonomous University of Mexico
Eun-Yi Moon, Sejong University
Ezio Laconi, University of Cagliari
Fabio Marongiu, University of Cagliari
Fahd Al-Mulla, Kuwait University
Ferdinando Chiaradonna, University of Milano-Bicocca
Firouz Darroudi, College of North Atlantic
Francis Martin, Lancaster University
Frederik Van Schooten, Maastricht University
Gary Goldberg, Rowan University School of Osteopathic Medicine
Gerard Wagemaker, Hacettepe University
Gladys Nangami, Meharry Medical College
Gloria Calaf, Columbia University
Graeme Williams, University of Reading
Gregory Wolf, University of Michigan
Gudrun Koppen, Flemish Institute for Technological Research
Gunnar Brunborg, Norwegian Institute of Public Health
H. Kim Lyerly, Duke University
Harini Krishnan, Rowan University School of Osteopathic Medicine
NOTE: Additional authors not added to this profile.

Document Type

Article

Version Deposited

Published Version

Publication Date

6-1-2015

Publication Title

Carcinogenesis

DOI

10.1093/carcin/bgv039

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.

Comments

The publisher will deposit in PubMed Central on behalf of NIH authors.

This article has been corrected. See Carcinogenesis. 2016 March; 37(3): 344.

Recommended Citation

Goodson WH, Lowe L, Carpenter DO, Gilbertson M, et al. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead. Carcinogenesis. 2015 Jun;36 Suppl 1:S254-96. doi: 10.1093/carcin/bgv039. PMID: 26106142. PMCID: PMC4480130.

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License