The effect of dietary selenium deficiency on acute colorectal mucosal nucleotoxicity induced by several carcinogens in the rodent

BACKGROUND: Selenium (SE) has been inversely associated with colon cancer risk. Two potential mechanisms of this effect were examined in a rodent short-term carcinogenesis assay: whether dietary SE deficiency altered the initiation aspect of carcinogenesis in the colon, and whether SE altered carcinogen metabolism. SETTING: Animal laboratory. SUBJECTS: 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. ENDPOINTS: Weight, serum SE concentration, and karryorhectic index (KI), which 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 metabolite, methylazoxymethanol (MAM), or 0.9% sodium chloride. Twenty-four hours after injection the colons were removed, blood drawn, and the stained colons assayed for nuclear aberrations. RESULTS: No weight differences were generated by the dietary variations. Low-dietary SE resulted 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 increased the KI in both the left and right colon. A SE-deficient diet was associated with a higher KI in both carcinogen groups in the right colon, with statistical significance for both the left and right colon in the MAM injection group. CONCLUSIONS: Dietary SE deficiency is associated with increased KI of the colon in MAM treated rats, SE, therefore, has a protective effect in the initiation phase of carcinogenesis.