THE EFFECT OF DIETARY SELENIUM DEFICIENCY ON ACUTE COLORECTAL MUCOSALNUCLEOTOXICITY INDUCED BY SEVERAL CARCINOGENS IN THE RODENT

BACKGROUND: Selenium (SE) has been inversely associated with colon can cer risk. Two potential mechanisms of this effect were examined in a r odent short-term carcinogenesis assay: whether dietary SE deficiency a ltered the initiation aspect of carcinogenesis in the colon, and wheth er SE altered carcinogen metabolism. SETTING: Animal laboratory. SUBJE CTS: 52 Sprague-Dawley rats, divided into a SE diet deficient group (0 .002 parts per million; ppm) and a SE sufficient (0.2 ppm) group. ENDP OINTS: Weight, serum SE concentration, and karryorhectic index (KI), w hich is a measure of acute carcinogen induced nuclear toxicity in the colonic mucosa. METHODS: After three weeks of acclimation to the diets , eight animals from each dietary group were injected with one of the following: dimethylhydrazine (DMH), a colon-specific carcinogen, its m etabolite, methylazoxymethanol (MAM), or 0.9% sodium chloride. Twenty- four hours after injection the colons were removed, blood drawn, and t he stained colons assayed for nuclear aberrations. RESULTS: No weight differences were generated by the dietary variations. Low-dietary SE r esulted in serum SE declining markedly in the study period to 6 ng/ml versus 33 ng/ml in the SE sufficient group. Diet alone, and variations in weight gain, did not alter the KI. Both carcinogens greatly increa sed the KI in both the left and right colon. A SE-deficient diet was a ssociated with a higher KI in both carcinogen groups in the right colo n, with statistical significance for both the left and right colon in the MAM injection group. CONCLUSIONS: Dietary SE deficiency is associa ted with increased KI of the colon in MAM treated rats, SE, therefore, has a protective effect in the initiation phase of carcinogenesis.