CONSIDERATION OF THE USE OF 17-BETA-N,N-DIETHYLCARBAMOYL-4-METHYL-4-AZA-5-ALPHA-ANDROSTAN-3-ONE (4MA), A 5-ALPHA-REDUCTASE INHIBITOR, IN PROSTATE-CANCER THERAPY

We investigated the effect of 17-beta-N,N-diethyl carbamoyl-4-methyl-4aza-5-alpha-androstan-3-one (4MA), a 5-alpha-reductase inhibitor, on growth inhibition of androgen-sensitive rat prostatic tumour (R3327-H) and correlated it with changes in weight of normal androgen target tissues and with levels of androgens. Groups of male Copenhagen rats were treated for 28 days with a daily injection of various, increasing doses of 4MA (0.01-4.0 mg/day) and the results were compared with control (vehicle-treated) and with castrated animals. 4MA decreased which was reflected in a decreased incorporation of BrdUrd in DNA of glandular epithelial cells in the tumour. Normal prostate wet weight was also decreased levels were not affected by 4MA treatment. Contrary to expectations, however, tissue levels of dihydrotestosterone in tumour and ventral prostate were still considerable purely due to 5-alpha-reductase inhibition. On the other hand, it was not possible to demonstrate any direct tumoricidal effect of 4MA in vitro. The relevance of these findings in terms of the endocrine mechanism of action of 4MA on tumour growth is discussed.