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Effects of Selenium on 7,12-Dimethylbenz(a)anthracene-induced Mammary Carcinogenesis and DNA Adduct Formation¹

Department of Breast Surgery and Breast Cancer Research Unit, Roswell Park Memorial Institute, Buffalo, New York 14263 [C. I.], and Health Effects Research Laboratory, United States Environmental Protection Agency, Cincinnati, Ohio 45268 [F. B. D.]

The purpose of the present investigation was to determine the effects of dietary selenium deficiency or excess on 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary neoplasia in rats and to delineate whether selenium-mediated modification of mammary carcinogenesis was associated with changes in carcinogen:DNA adduct formation and activities of liver microsomal enzymes that are involved in xenobiotic metabolism. Female Sprague-Dawley rats were divided into three groups from weaning and were maintained on one of three synthetic diets designated as follows: (a) selenium deficient (<0.02 ppm); (b) selenium adequate (0.2 ppm); or (c) selenium excess (2.5 ppm). For the DMBA binding and DNA adduct studies, rats were given a dose of [³H]DMBA p.o. after 1 month on their respective diets. Results from the liver and the mammary gland indicated that neither selenium deficiency nor excess had any significant effect on the binding levels, which were calculated on the basis of total radioactivity isolated with the purified DNA. Furthermore, it was found that dietary selenium intake did not seem to affect quantitatively or qualitatively the formation of DMBA:DNA adducts in the liver. Similarly, in a parallel group of rats that did not receive DMBA, the activities of aniline hydroxylase, aminopyrine N-demethylase, and cytochrome c reductase were not significantly altered by dietary selenium levels. Concurrent with the above experiments, the effect of dietary selenium intake on carcinogenesis was also monitored. Results of this experiment indicated that selenium deficiency enhanced mammary carcinogenesis only when this nutritional condition was maintained in the postinitiation phase. Likewise, an excess of selenium intake inhibited neoplastic development only when this regimen was continued after DMBA administration. In either case, deficient or excess selenium at the time of carcinogenic insult failed to produce a significant effect on subsequent tumor yield, if selenium intake was returned to normal during the proliferative phase of tumor growth. Based on the results of these studies, it is suggested that selenium-mediated modification of mammary tumorigenesis is not exerted via alterations in carcinogenic initiation (i.e., metabolism or DNA adduct formation).

¹ This work was supported by Grant CA 27706 from the National Cancer Institute, NIH, Department of Health and Human Services, and the United States Environmental Protection Agency Health Effects Research Laboratory.

² To whom requests for reprints should be addressed.

³ Present address: Experimental Toxicology Branch, National Institute for Occupational Health and Safety, 4676 Columbia Parkway, Cincinnati, OH 45226.

Received 5/24/84. Accepted 9/21/84.

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