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Title: Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: The challenge ahead
Authors: 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
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
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Jun-2015
Citation: Carcinogenesis. Vol.36, (2015), S254-S296
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.
ISSN: 14602180
Appears in Collections:Scopus 2011-2015

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