Molecular Pharmacology, Vol 14, 1156-1166, Copyright © 1978 by the American Society for Pharmacology and Experimental Therapeutics

Inhibition of SV40 DNA Synthesis by Camptothecin and Neocarzinostatin

¹ Departments of Molecular Pharmacology and Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461

Both camptothecin and neocazinostatin cause 50% inhibition of simian virus 40 DNA synthesis in BSC-1 cells at a drug concentration of 1-0.1 µM. Uniformly prelabeled Form I simian virus 40 DNA is not converted to Form II by 100 µM camptothecin or 10 µM (10 µg/ml) neocarzinostatin, despite extensive drug-induced breakage of cellular DNA at these concentrations. Kinetic experiments examined the fate of replicative intermediates at the onset of inhibition of DNA synthesis. In the presence of 100 µg/ml neocarzinostatin, label proceeds through replicative intermediate molecules and is found largely (>75%) as Form I simian virus 40 DNA. At 100 µM camptothecin, up to 50% of newly made simian virus 40 DNA is found as a Form II-like species.

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ACKNOWLEDGMENTS The authors thank Drs. M. Horwitz, S. Baum, and R. Burger for their helpful discussions.