Mechanisms of PCBS-Induced Breast Cancer.
Abstract
Our research is aimed at the Investigation of the effects of polychiorinated biphenyls (PCBs) in breast cancer. PCBs are industrial chemicals which persist in our environment. The lipophilicity of PCBs and their tendency to bioaccumulate in adipose tissue and breast milk raise concern about the health risks associated with exposure to PCBs and related compounds. Commercial PCB mixtures are complete carcinogens, producing hepatocellular carcinomas in rats and mice, but the mechanisms by which they do so have not been determined. We and others have shown that higher halogenated FOBs (especially, tetra-, penta-, and hexa- chlorinated biphenyls) act as promoters of carcinogenesis, but their initiating or DNA damaging activity has not been conclusively demonstrated. In our original proposal we presented considerable data to support the concept that the lower halogenated biphenyls may be activated by hepatic and breast (milk) enzymes to oxygenated species that are electrophilic and bind to DNA. Of particular interest were the quinone metabolites. Our data showed that PCBs are metabolized to dihydroxy metabolites, that these can be oxidized by peroxidases (including lactoperoxidase) and prostaglandin synthase to quinones, that these PCB-quinones are strong electrophiles that react with both sulfur and nitrogen nucleophiles, including nucleotides and DNA. We offered preliminary observations that supported the concept that PCB quinones redox cycle.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1997
- Accession Number
- ADA337821
Entities
People
- Larry W. Robertson
Organizations
- University of Kentucky