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

Autores: Goodson III, W. H. (Autor de correspondencia); Lowe, L.; Carpenter, D. O.; Gilbertson, M.; Manaf Ali, A.; López de Cerain Salsamendi, Adela; Lasfar, A.; Carnero, A.; Azqueta Oscoz, Amaya; Amedei, A.; Charles, A. K.; Collins, A. R.; Ward, A.; Salzberg, A. C.; Colacci, A.; Olsen, A. K.; Berg, A.; Barclay, B. J.; Zhou, B. P.; Blanco-Aparicio, C.; Baglole, C.; Dong, C.; Mondello, C.; Hsu Ch, W.; Naus, C. C.; Yedjou, C.; Curran, C. S.; Laird, D. W.; Koch, D. C.; Carlin, D. J.; Felsher, D. W.; Roy, D.; Brown, D.; Ratovitski, E.; Ryan, E. P.; Corsini, E.; Rojas, E.; Moon, E. Y.; Laconi, E.; Marongiu, F.; Al-Mulla, F.; Chiaradonna, F.; Darroudi, F.; Martin, F. L.; Van Schooten, F. J.; Goldberg, G. S.; Wagemaker, G.; Nangami, G.; Rice, G.; Calaf, G. M.
Título de la revista: CARCINOGENESIS
ISSN: 0143-3334
Volumen: 36
Número: Supl. 1
Páginas: S254 - S296
Fecha de publicación: 2015
Resumen:
Low-dose exposures to common environmental chemicals that are deemed safe individually may be combining to instigate carcinogenesis, thereby contributing to the incidence of cancer. This risk may be overlooked by current regulatory practices and needs to be vigorously investigated.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 relate
DOI: https://doi.org/10.1093/carcin/bgv039
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