DeAngelo Anthony B, Geter David R, Rosenberg Daniel W, Crary C Ken, George Michael H
National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency MD-68, Research Triangle Park, NC 27711, USA.
Cancer Lett. 2002 Dec 10;187(1-2):25-31. doi: 10.1016/s0304-3835(02)00356-7.
Bromodichloromethane (BDCM) and bromoform (TBM) have been demonstrated to be colon carcinogens in male and female F344/N rats following administration by corn oil gavage. Our chronic bioassay of BDCM administered in the drinking water failed to demonstrate colon cancer in male F344/N rats. In the present study we addressed the capability of trihalomethanes (THMs) administered in drinking water to induce aberrant crypt foci (ACF), early putative preneoplastic lesions, in the colons of male F344/N rats and B6C3F(1) mice. BDCM was tested in the A/J mouse strain. Rats and B6C3F(1) mice were exposed to isomolar concentrations of the THMs [0.5 g/l chloroform (TCM), 0.7 g/l BDCM, 0.9 g/l dibromochloromethane (DBCM), or 1.1 g/l (TBM)] for 13 weeks. A/J mice were exposed to 0.5 g/l BDCM in the drinking water for 13 and 30 weeks. Deionized water and 0.25% Alkamuls EL-620 were the negative and vehicle controls. ACF incidence (percent) and number (ACF/colon) for the rat were: combined controls, 0; AOM, 100%, 27.17+/-6.28 (P<0.01); TCM, 16.7%, 0.17+/-0.17; BDCM, 83.3%, 1.50+/-0.56 (P<0.01); DBCM, 50%, 1.17+/-0.65 (P<0.01); TBM, 66.7%, 1.17+/-0.40 (P<0.01). THM-induced ACF primarily occurred in the rectal segment of the colon (92%). No ACF were observed in the colons of B6C3F(1) mice following 13 weeks of THM treatment or in the colons of A/J mice following 13 and 30 weeks of BDCM exposure. These studies demonstrate that brominated THMs administered in the drinking water significantly induced preneoplastic ACF in the colon of rats.