The induction of aberrant crypt foci (ACF) in the colons of rats by trihalomethanes administered in the drinking water

Abstract

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.