Selective distribution of selenium in colon parallels its antitumor activity.

Results of epidemiologic and experimental studies suggest that selenium can inhibit the development of tumors. In rats, the administration of selenium decreases the incidence of carcinogen-induced colon tumors; the inhibition is greater in the proximal colon that in the distal colon. We investigated the distribution of selenium in the different segments of rat colon and determined the uptake of selenium in the mucosa and in the muscle layers of each segment. The colon was perfused before removal of the segments to ensure complete removal of blood-borne selenium. We found that the concentration of selenium was greater in the proximal colon than in the distal colon and that within each segment the uptake was higher in mucosa than in muscle. In addition, we determined the level of selenium in blood, serum, and liver at different times after the administration of various doses of selenium. Though the mechanism by which selenium prevents tumor development is unknown, the data indicate a correlation between the uptake of selenium in different segments of colon and inhibition of tumorigenesis.

Selenium and the acute effects of the carcinogens, 2-acetylaminofluorene and methylazoxymethanol acetate.

Selenium inhibits the development of 2-acetylaminofluorene-induced hepatic tumors and methylazoxymethanol-induced colon tumors. It has been suggested that selenium exerts these protective effects by inhibiting metabolic activation of the carcinogen. We have studied the effects of selenium upon the acute inhibition of RNA and DNA synthesis induced by 2-acetylaminofluorene or methylazoxymethanol in intact liver, regenerating liver, and colon of weanling male Sprague-Dawley rats. Some animals received selenium in the drinking water (4 ppm) for 1 week, while others received a single injection of selenium (1 mg/kg i.p.) prior to being treated with the carcinogens. No protection against the effects of the carcinogens on RNA or DNA synthesis was noted with either treatment of selenium. Disulfiram did protect against the 2-acetylaminofluorene-induced inhibition of hepatic RNA synthesis, and pyrazole prevented the inhibition of RNA synthesis induced by methylazoxymethanol in both liver and colon. Serum selenium levels are reported. The data indicate that selenium does not influence the acute alterations induced by the carcinogens 2-acetylaminofluorene or methylazoxymethanol and suggest that the tumor-preventive effects of selenium are probably due to a mechanism other than interference with carcinogen activation and interaction with cellular macromolecules.