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Journal Articles Carcinogenesis Year : 2015

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

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Leroy Lowe
  • Function : Author
Abdul Manaf Ali
  • Function : Author
Ahmed Lasfar
  • Function : Author
Amancio Carnero
  • Function : Author
Amaya Azqueta
  • Function : Author
  • PersonId : 987383
Amedeo Amedei
  • Function : Author
Andrew Ward
  • Function : Author
Anna C Salzberg
  • Function : Author
Ann-Karin Olsen
  • Function : Author
Arthur Berg
  • Function : Author
Barry J Barclay
  • Function : Author
Binhua P Zhou
  • Function : Author
Chenfang Dong
  • Function : Author
Chiara Mondello
  • Function : Author
Chia-Wen Hsu
  • Function : Author
Clement Yedjou
  • Function : Author
Dale W Laird
  • Function : Author
Daniel C Koch
  • Function : Author
Dean W Felsher
  • Function : Author
Debasish Roy
  • Function : Author
Dustin G Brown
  • Function : Author
Emilio Rojas
  • Function : Author
Eun-Yi Moon
  • Function : Author
Ezio Laconi
  • Function : Author
Fabio Marongiu
  • Function : Author
Fahd Al-Mulla
  • Function : Author
Firouz Darroudi
  • Function : Author
Gary S Goldberg
  • Function : Author
Gloria M Calaf
  • Function : Author
Graeme Williams
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Gregory T Wolf
  • Function : Author
Gudrun Koppen
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Gunnar Brunborg
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H Kim Lyerly
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Harini Krishnan
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Hasiah Ab Hamid
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Hemad Yasaei
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Hideko Sone
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Hiroshi Kondoh
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Hosni K Salem
  • Function : Author
Hsue-Yin Hsu
  • Function : Author
Hyun Ho Park
  • Function : Author
Igor Koturbash
  • Function : Author
James E Klaunig
  • Function : Author
Jan Vondráček
  • Function : Author
Jayadev Raju
  • Function : Author
Jesse Roman
  • Function : Author
Jordan Woodrick
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Josiah Ochieng
  • Function : Author
Judith Weisz
  • Function : Author
Jun Sun
Kim Moorwood
  • Function : Author
Laura Soucek
  • Function : Author
Le Jian
  • Function : Author
Liang-Tzung Lin
  • Function : Author
Lin Li
Linda Gulliver
  • Function : Author
Lisa J Mccawley
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Lorenzo Memeo
  • Function : Author
Louis Vermeulen
  • Function : Author
Luc Leyns
  • Function : Author
Luoping Zhang
  • Function : Author
Mahara Valverde
  • Function : Author
Mahin Khatami
  • Function : Author
Marc A Williams
  • Function : Author
Mark Wade
  • Function : Author
Menghang Xia
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Monica Vaccari
  • Function : Author
Neetu Singh
  • Function : Author
Nuzhat Ahmed
  • Function : Author
Pankaj Vadgama
  • Function : Author
Paul Dent
  • Function : Author
Petr Heneberg
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Philippa Darbre
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Po Sing Leung
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R Brooks Robey
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Rabindra Roy
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Ranjeet K Sinha
  • Function : Author
Rekha Mehta
  • Function : Author
Renza Vento
  • Function : Author
Rita Nahta
  • Function : Author
Sakina E Eltom
  • Function : Author
Samira A Brooks
  • Function : Author
Sandra Ryeom
  • Function : Author
Sandra S Wise
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Sarah N Bay
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Simona Romano
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Sofia Pavanello
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Stefano Forte
  • Function : Author
Tae-Jin Lee
  • Function : Author
Takemi Otsuki
  • Function : Author
Tao Chen
  • Function : Author
Tove Hultman
  • Function : Author
Valérian Dormoy
Yon Rojanasakul
  • Function : Author
Yunus Luqmani
  • Function : Author
Zhenbang Chen
  • Function : Author
Zhiwei Hu
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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.
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Dates and versions

pasteur-01352152 , version 1 (05-08-2016)

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Attribution - NonCommercial - CC BY 4.0

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William H Goodson, Leroy Lowe, David O Carpenter, Michael Gilbertson, Abdul Manaf Ali, et al.. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.. Carcinogenesis, 2015, 36 (Suppl 1), pp.S254-96. ⟨10.1093/carcin/bgv039⟩. ⟨pasteur-01352152⟩
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