Effect of 20-methylcholanthrene on DNA synthesis in mouse prostates grown in vitro

Abstract

Ventral prostate glands of C 3H mice were grown in vitro in normal medium and in medium containing 4 μg per ml of 20-methylcholanthrene. The explants were labelled with [8- 14C]-adenine after 4, 7 and 10 days' treatment and fixed 5 or 24 hours later. Autoradiographs of unextracted slides or slides from which the RNA had been removed with ribonuclease or cold perchloric acid were prepared. Untreated sections of controls show incorporation of adenine in both epithelium and fibroblasts. In explants exposed to the carcinogen the distribution of labelled cells in the alveolar epithelium is similar to that in the controls; labelled fibroblasts are still found after 4 days' treatment, but at 7 and 10 days they are unlabelled. Autoradiographs of sections treated with ribonuclease or cold perchloric acid can be assumed to be due to labelled DNA. In controls, epithelium and fibroblasts are labelled; in MC treated explants epithelial cells only are labelled while DNA synthesis by fibroblasts is inhibited after more than 4 days' treatment. Cell counts show that after 4 days' treatment with the carcinogen the percentage of epithelial cells synthesizing DNA is equal to that in controls although the mitotic index is doubled; after 7–10 days the percentage of synthesizing cells increases by 40 per cent in the treated explants, but the mitotic index rises to 3–4 times the control value. It is suggested that some cells in the controls synthesize DNA without proceeding to division and that these cells are forced into division by 20-methylcholanthrene.