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, 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

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

Additional authors (#56 - 133) not listed in entry.

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.

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