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Selenium and the Acute Effects of the Carcinogens, 2-Acetylaminofluorene and Methylazoxymethanol Acetate¹

Laboratory of Pharmacology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021

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.

¹ Supported by USPHS Grants CA 08748 from the National Cancer Institute and CA 15637 from the National Cancer Institute through the National Large Bowel Cancer Project.

² Research Fellow, Department of Surgery, Memorial Sloan-Kettering Cancer Center, and Cornell University Medical College, New York, N. Y.

³ To whom requests for reprints should be addressed.

Received 12/ 3/81. Accepted 4/30/82.

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