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Induction of Transitional Cell Hyperplasia in the Urinary Bladder and Aberrant Crypt Foci in the Colon of Rats Treated with Individual and a Mixture of Drinking Water Disinfection By-Products

Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina 27599

Sundeep Chandra

Experimental Pathology Laboratories, Inc., Research Triangle Park, North Carolina 27709

Michelle J. Hooth

Environmental Carcinogenesis Division, National Health and Environmental Effects Research Laboratory (NHEERL), U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711

Susan D. Hester

Environmental Carcinogenesis Division, National Health and Environmental Effects Research Laboratory (NHEERL), U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711

Robert Schoonhoven

Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, North Carolina 27599

Douglas C. Wolf

Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina 27599, wolf.doug{at}epamail.epa.gov, Environmental Carcinogenesis Division, National Health and Environmental Effects Research Laboratory (NHEERL), U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711

Cancer of the urinary bladder and colon are significant human health concerns. Epidemiological studies have suggested a correlation between these cancers and the chronic consumption of chlorinated surface water containing disinfection by-products (DBPs). The present study was designed to determine if exposure to DBPs would cause preneoplastic or neoplastic lesions in the urinary bladder and colon of rats, and what effect a mixture of DBPs would have on these lesions. Male and female Eker rats were treated via drinking water with low and high concentrations of potassium bromate, 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), chloroform, or bromodichloromethane individually or in a mixture for 10 months. The urinary bladders and colons were examined for the presence of preneoplastic lesions. Cell proliferation in the urothelium was examined using immunohistochemical staining for bromodeoxyuridine. Aberrant crypt foci (ACF), as well as the number of individual crypts in each ACF, were identified and counted microscopically after staining with 0.2% methylene blue. Colon crypt cell proliferation and mitotic index were determined using immunohistochemical staining for proliferating cell nuclear antigen. Labeling indexes for the urinary bladder and colon were calculated based on the percentage of positively labeled cells. Treatment with the high dose of MX caused transitional epithelial hyperplasia and cell proliferation in the rat urinary bladder, and this effect was diminished in the high dose mixture animals. Treatment with 4 individual DBPs, as well as a mixture of them, caused the development of ACF, the putative preneoplastic lesion of colon cancer.

Key Words: Rat • urinary bladder • colon • aberrant crypt foci • water • disinfection by-products • cell proliferation.

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