Reversible Inhibition of DNA Synthesis in Hamster Embryo Cells in Culture: Action of 1,2-Benzanthracene and 7,12-Dimethylbenz(a)anthracene

Summary

The effects of the relatively weak carcinogen, 1,2-benzanthracene (BA), and its potent carcinogenic derivative, 7,12-dimethylbenz(a)anthracene (DMBA), on the resumption of DNA synthesis in Syrian hamster embryo cells blocked in the S phase of the mitotic cycle, were analyzed. A maximum level of binding of BA to DNA (1.08 molecule/200,000 nucleotide units) occurred after 4 hours of treatment of cells which had been released from thymidine blockage with 10^-4 m deoxycytidine. The binding of this level of BA appeared to have little if any effect on the movement of cells from the DNA replicative phase into mitosis. In contrast, DMBA produced an immediate suppression in the rate of DNA synthesis, which is normally resumed within minutes after release under control conditions or BA treatment. Furthermore, DMBA reduced the mitotic activity by 50% at 4 hours and the maximal level of binding to DNA (0.7 molecule/200,000 nucleotide units) occurred only after 24 hours of treatment. It was shown that BA exerted a protective action against the suppressive activity of DMBA on DNA synthesis and the movement of cells into mitosis. The binding of DMBA-³H to DNA was almost abolished (97% at 2 hours, 92% at 4 hours) in the presence of an equimolar concentration of BA. Two possibilities are suggested for the mechanism of BA protection against DMBA action.