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STUDIES OF DBP-INDUCED COLON CANCER
Impact/Purpose:
The objectives of this project are to: use drinking water studies to investigate the development of this cancer in rats from preneoplastic lesions (aberrant crypt foci [ACF]) through progression to carcinoma; to determine the relative potency of ACF induction by the different THMs; to examine the carcinogenicity of a mixture of THMs with higher concentrations of brominated congeners; and to assess the role of dietary fat content in THM-induced colon cancer.
Description:
Induction of colon carcinomas by trihalomethanes in rats may be relevant to epidemiological findings of increased incidences of colon-rectal cancer associated with exposure to chlorination byproducts. These studies have demonstrated that the brominated THMs in drinking water induce ACF with a relative potency that is identical to their GST-theta-mediated mutagenic potency. Bromoform and dibromochloromethane are particularly potent, and the mixture containing higher concentrations of these THMs was also effective in producing the prenoplastic lesions.
A new class of DBPs, halonitromethanes, have recently been identified in drinking water, and these compounds are potent genotoxicants in bacteria and eucaryotic cells. These compounds will also be tested for colon ACF-inducing capability and their ability to modify DNA in the colon.