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PROMOTION OF TRIHALOMETHANE-INDUCED COLON, ABERRANT CRYPT FOCI (ACF) BY A HIGH FAT DIET
George, M H., S. Kilburn, T. Moore, AND A B. DeAngelo. PROMOTION OF TRIHALOMETHANE-INDUCED COLON, ABERRANT CRYPT FOCI (ACF) BY A HIGH FAT DIET. Presented at Society of Toxicology, Nashville, TN, 03/17-20/2002.
Bromodichloromethane (BOCM) and tribromomethane (TBM) enhanced neoplasia in the large intestine of rats when given by corn oil gavage; BOCM in the drinking water to male rats did not induce colon tumors, but did increase liver tumors. However, TBM and a mixture of THMs high in brominated trihalomethanes (THMs) induced colon neoplasia after 52 weeks. We found that brominated THMs induced ACF, putative preneoplastic lesions, in the colon when included in the drinking water of male rats. This study was undertaken to determine if the ACF can be promoted by a diet high in fat. Male F344/N rats were exposed to isomolar concentrations of the THMs: 0.5,0.7 ,0.9 and 1.1 g/L of chloroform (TCM), DBCM, dibromochloromethane (DBCM) and TBM in the drinking water. Emulphor (0.25%) and 15 mg azoxymethane/kg ip (A OM) were the vehicle and positive control groups. Animals from each treatment group were fed the HF diet (Purina 5001; 19% fat). Groups from the emulphor, AOM, and BDCM treatments were given corn oil (0.5 mi/kg, po) 5 days/week. After 26 weeks the colons were examined for ACF. There was a statistically significant positive association between the ACF/colon (:t SD) and the number of bromine atoms on the THM molecule: 0.25% emulphor (0), TCM (0.67 :t 0.75), BDCM ( 1.33 :t 1.11 ), DBCM (2.67 :t 2.36) and TBM (2.83 :t 2.34 ). AOM treated animals had 23.17 :t 7.75 ACF/colon. Corn oil did not increase the ACF/colon in the vehicle control or BDCM treatment groups, but did in the A OM group (32.5 :t 9.0). The HF fat diet was effective in promoting only the ACF induced by TBM (5.33 :t 2.26). The same result was found for the total number of crypts/colon. The data suggest a fundamental difference between TBM-induced ACF and those induced by the other THMs, a difference that might help to explain the ability of TBM, and not BDCM to induce colon neoplasia when administered chronically in the drinking water.
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Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
ENVIRONMENTAL CARCINOGENESIS DIVISION
CANCER BIOLOGY BRANCH