Inhibition of SV40 DNA synthesis by camptothecin and neocarzinostatin

Both camptothecin and neocarzinostatin 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.