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

Publication ,  Journal Article
Goodson, WH; Lowe, L; Carpenter, DO; Gilbertson, M; Manaf Ali, A; Lopez de Cerain Salsamendi, A; Lasfar, A; Carnero, A; Azqueta, A; Amedei, A ...
Published in: Carcinogenesis
June 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.

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Published In

Carcinogenesis

DOI

EISSN

1460-2180

Publication Date

June 2015

Volume

36 Suppl 1

Issue

Suppl 1

Start / End Page

S254 / S296

Location

England

Related Subject Headings

  • Oncology & Carcinogenesis
  • Neoplasms
  • Humans
  • Hazardous Substances
  • Environmental Exposure
  • Carcinogens, Environmental
  • Carcinogenesis
  • Animals
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
 

Citation

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Goodson, W. H., Lowe, L., Carpenter, D. O., Gilbertson, M., Manaf Ali, A., Lopez de Cerain Salsamendi, A., … Hu, Z. (2015). Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead. Carcinogenesis, 36 Suppl 1(Suppl 1), S254–S296. https://doi.org/10.1093/carcin/bgv039
Goodson, William H., Leroy Lowe, David O. Carpenter, Michael Gilbertson, Abdul Manaf Ali, Adela Lopez de Cerain Salsamendi, Ahmed Lasfar, et al. “Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.Carcinogenesis 36 Suppl 1, no. Suppl 1 (June 2015): S254–96. https://doi.org/10.1093/carcin/bgv039.
Goodson WH, Lowe L, Carpenter DO, Gilbertson M, Manaf Ali A, Lopez de Cerain Salsamendi A, 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(Suppl 1):S254–96.
Goodson, William H., et al. “Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.Carcinogenesis, vol. 36 Suppl 1, no. Suppl 1, June 2015, pp. S254–96. Pubmed, doi:10.1093/carcin/bgv039.
Goodson WH, Lowe L, Carpenter DO, Gilbertson M, Manaf Ali A, Lopez de Cerain Salsamendi A, Lasfar A, Carnero A, Azqueta A, Amedei A, Charles AK, Collins AR, Ward A, Salzberg AC, Colacci A, Olsen A-K, Berg A, Barclay BJ, Zhou BP, Blanco-Aparicio C, Baglole CJ, Dong C, Mondello C, Hsu C-W, Naus CC, Yedjou C, Curran CS, Laird DW, Koch DC, Carlin DJ, Felsher DW, Roy D, Brown DG, Ratovitski E, Ryan EP, Corsini E, Rojas E, Moon E-Y, Laconi E, Marongiu F, Al-Mulla F, Chiaradonna F, Darroudi F, Martin FL, Van Schooten FJ, Goldberg GS, Wagemaker G, Nangami GN, Calaf GM, Williams G, Wolf GT, Koppen G, Brunborg G, Lyerly HK, Krishnan H, Ab Hamid H, Yasaei H, Sone H, Kondoh H, Salem HK, Hsu H-Y, Park HH, Koturbash I, Miousse IR, Scovassi AI, Klaunig JE, Vondráček J, Raju J, Roman J, Wise JP, Whitfield JR, Woodrick J, Christopher JA, Ochieng J, Martinez-Leal JF, Weisz J, Kravchenko J, Sun J, Prudhomme KR, Narayanan KB, Cohen-Solal KA, Moorwood K, Gonzalez L, Soucek L, Jian L, D’Abronzo LS, Lin L-T, Li L, Gulliver L, McCawley LJ, Memeo L, Vermeulen L, Leyns L, Zhang L, Valverde M, Khatami M, Romano MF, Chapellier M, Williams MA, Wade M, Manjili MH, Lleonart ME, Xia M, Gonzalez MJ, Karamouzis MV, Kirsch-Volders M, Vaccari M, Kuemmerle NB, Singh N, Cruickshanks N, Kleinstreuer N, van Larebeke N, Ahmed N, Ogunkua O, Krishnakumar PK, Vadgama P, Marignani PA, Ghosh PM, Ostrosky-Wegman P, Thompson PA, Dent P, Heneberg P, Darbre P, Sing Leung P, Nangia-Makker P, Cheng QS, Robey RB, Al-Temaimi R, Roy R, Andrade-Vieira R, Sinha RK, Mehta R, Vento R, Di Fiore R, Ponce-Cusi R, Dornetshuber-Fleiss R, Nahta R, Castellino RC, Palorini R, Abd Hamid R, Langie SAS, Eltom SE, Brooks SA, Ryeom S, Wise SS, Bay SN, Harris SA, Papagerakis S, Romano S, Pavanello S, Eriksson S, Forte S, Casey SC, Luanpitpong S, Lee T-J, Otsuki T, Chen T, Massfelder T, Sanderson T, Guarnieri T, Hultman T, Dormoy V, Odero-Marah V, Sabbisetti V, Maguer-Satta V, Rathmell WK, Engström W, Decker WK, Bisson WH, Rojanasakul Y, Luqmani Y, Chen Z, Hu Z. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead. Carcinogenesis. 2015 Jun;36 Suppl 1(Suppl 1):S254–S296.
Journal cover image

Published In

Carcinogenesis

DOI

EISSN

1460-2180

Publication Date

June 2015

Volume

36 Suppl 1

Issue

Suppl 1

Start / End Page

S254 / S296

Location

England

Related Subject Headings

  • Oncology & Carcinogenesis
  • Neoplasms
  • Humans
  • Hazardous Substances
  • Environmental Exposure
  • Carcinogens, Environmental
  • Carcinogenesis
  • Animals
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis