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

Issued Date

2015-06-01

Resource Type

Article

ISSN

14602180
01433334

DOI

10.1093/carcin/bgv039

Other identifier(s)

2-s2.0-84937708474

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

Carcinogenesis. Vol.36, (2015), S254-S296

Suggested Citation

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, Edward Ratovitski, Elizabeth P. Ryan, Emanuela Corsini, Emilio Rojas, Eun Yi Moon, Ezio Laconi, Fabio Marongiu, Fahd Al-Mulla, Ferdinando Chiaradonna, Firouz Darroudi, Francis L. Martin, Frederik J. Van Schooten, Gary S. Goldberg, Gerard Wagemaker, Gladys 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, Luoping Zhang Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: The challenge ahead. Carcinogenesis. Vol.36, (2015), S254-S296. doi:10.1093/carcin/bgv039 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/35451

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Title

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

Author(s)

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
 Edward Ratovitski
 Elizabeth P. Ryan
 Emanuela Corsini
 Emilio Rojas
 Eun Yi Moon
 Ezio Laconi
 Fabio Marongiu
 Fahd Al-Mulla
 Ferdinando Chiaradonna
 Firouz Darroudi
 Francis L. Martin
 Frederik J. Van Schooten
 Gary S. Goldberg
 Gerard Wagemaker
 Gladys 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
 Luoping Zhang

Other Contributor(s)

Getting to Know Cancer
 Lancaster University
 University at Albany State University of New York
 Getting to Know Cancer
 Universiti Sultan Zainal Abidin
 Universidad de Navarra
 Rutgers Biomedical and Health Sciences
 Hospital Universitario Virgen del Rocio
 Universita degli Studi di Firenze
 University of Reading
 Universitetet i Oslo
 University of Bath
 Penn State College of Medicine
 Environmental Protection and Health Prevention Agency
 Norwegian Institute of Public Health
 National Research Council Canada
 University of Kentucky
 Centro Nacional de Investigaciones Oncologicas
 McGill University
 Consiglio Nazionale delle Ricerche
 National Center for Advancing Translational Sciences
 The University of British Columbia
 Jackson State University
 University of Wisconsin Madison
 Western University
 Stanford University School of Medicine
 National Institute of Environmental Health Sciences
 City University of New York
 Colorado State University
 The Johns Hopkins School of Medicine
 Universita degli Studi di Milano
 Universidad Nacional Autonoma de Mexico
 Sejong University
 Universita degli Studi di Cagliari
 University of Kuwait
 University of Milano - Bicocca
 College of North Atlantic
 Maastricht University
 Rowan University
 Hacettepe Universitesi
 Meharry Medical College
 Columbia University Medical Center
 Universidad de Tarapaca de Arica
 University of Michigan Medical School
 Flemish Institute for Technological Research
 Duke University Medical Center
 Universiti Putra Malaysia
 Brunel University London
 National Institute for Environmental Studies of Japan
 Kyoto University Hospital
 Cairo University
 Tzu Chi University
 Yeungnam University
 University of Arkansas for Medical Sciences
 Indiana University
 Academy of Sciences of the Czech Republic
 Toxicology Research Division
 University of Louisville
 Louisville Veterans Administration Medical Center
 University of Southern Maine
 Vall d`Hebron Institut de Oncologia
 Lombardi Comprehensive Cancer Center
 University of Cambridge
 Department of Cell Biology
 Rush University
 Oregon State University
 The Cancer Institute of New Jersey
 Vrije Universiteit Brussel
 Institucio Catalana de Recerca I Estudis Avancats
 Curtin University
 Department of Health Western Australia
 University of California, Davis
 Taipei Medical University
 Chinese University of Hong Kong
 University of Otago
 Vanderbilt University
 Mediterranean Institute of Oncology
 Academic Medical Centre, University of Amsterdam
 University of California, Berkeley
 National Cancer Institute
 Universita degli Studi di Napoli Federico II
 Centre de recherche en cancérologie de Lyon
 United States Army
 Istituto Italiano di Tecnologia
 California Pacific Medical Center

Abstract

© The Author 2015. 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.

Keyword(s)

Biochemistry, Genetics and Molecular Biology

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/35451

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Scopus 2011-2015