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

http://ir.library.oregonstate.edu/concern/articles/r781wh74k

This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Oxford University Press. The published article can be found at:  http://carcin.oxfordjournals.org/

The publisher and the author(s) have made this article open access.

Descriptions

Attribute NameValues
Creator
Abstract or Summary
  • 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.
Resource Type
DOI
Date Available
Date Issued
Citation
  • Goodson, W. H., Lowe, L., Carpenter, D. O., Gilbertson, M., Ali, A. M., de Cerain Salsamendi, A. L., ... & Hu, Z. (2015). Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead. Carcinogenesis, 36(Suppl 1), S254-S296. doi:10.1093/carcin/bgv039
Series
Rights Statement
Funding Statement (additional comments about funding)
Publisher
Peer Reviewed
Language
Replaces
Additional Information
  • description.provenance : Approved for entry into archive by Patricia Black(patricia.black@oregonstate.edu) on 2015-07-15T20:25:11Z (GMT) No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: bb87e2fb4674c76d0d2e9ed07fbb9c86 (MD5) BissonWilliamHEnvironmentalMolecularToxicologyAssessingCarcinogenicPotentialChallengeAhead.pdf: 1849206 bytes, checksum: 22ef814673a3d50df9f9e2ef1c2a9b9a (MD5)
  • description.provenance : Submitted by Patricia Black (patricia.black@oregonstate.edu) on 2015-07-15T20:24:44Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: bb87e2fb4674c76d0d2e9ed07fbb9c86 (MD5) BissonWilliamHEnvironmentalMolecularToxicologyAssessingCarcinogenicPotentialChallengeAhead.pdf: 1849206 bytes, checksum: 22ef814673a3d50df9f9e2ef1c2a9b9a (MD5)
  • description.provenance : Made available in DSpace on 2015-07-15T20:25:11Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: bb87e2fb4674c76d0d2e9ed07fbb9c86 (MD5) BissonWilliamHEnvironmentalMolecularToxicologyAssessingCarcinogenicPotentialChallengeAhead.pdf: 1849206 bytes, checksum: 22ef814673a3d50df9f9e2ef1c2a9b9a (MD5) Previous issue date: 2015-06

Relationships

Parents:

This work has no parents.

Last modified

Downloadable Content

Download PDF

Items