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Departments of Oncology [S. M., W. E. C.], Genetics and Human Genetics [K. J. S.], Human Nutrition and Food [W. E. C.], and Zoology [F. R. A.], Howard University Cancer Center, Washington, D. C. 20059
The role of androgens in the regulation of carcinogen metabolism in the renal tissue of BALB/c mice was investigated. Kidney microsomal enzyme preparations from mature and immature animals were used in mutagenic studies using the Arnes test. Androgen receptors (cytosolic and nuclear) were also evaluated. The results show that the microsomal enzymes from mature males had greater potential to biotransform dimethylnitrosamine than did the microsomal enzymes from mature females or immature animals. Testosterone treatment of mature females or immature animals resulted in a significant increase in the mutagenic ability of their renal microsomal enzymes. Androgen receptors were detected in kidney cytosols of mature and immature animals (both males and females); however, nuclear androgen receptors were detected only in the mature males. Testosterone treatment resulted in a significant accumulation of nuclear androgen receptors in the kidneys of mature females and immature animals. The relationships among mutagenic activity, androgen receptors, the levels of N-demethylase (an enzyme responsible for conversion of dimethylnitrosamine to its active metabolite), dietary fat, and the carcinogen metabolism are discussed.
1 Presented at the Workshop on Fat and Cancer, December 10 to 12, 1979, Bethesda, Md. Supported by National Cancer Institute Grant CA-14718 and NIH Grant 2S06 RR08016-10.
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