Incubation of camptothecin with HeLa cells in either the G1 or S phase of the cell cycle results in fragmentation of DNA as analyzed on alkaline sucrose gradients. Removal of the drug from G1- or S-phase cells results in the normal sedimentation of cellular DNA. Neither the fragmentation nor the repair of HeLa cell DNA requires DNA replication. However, subtle irreversible changes must take place in the DNA in cells treated with camptothecin for 30 min during the S phase, since such cells are unable to undergo subsequent cell division. The lethal effect is presumed to be at the single strand-replication forks.
This investigation was supported by USPHS Grants CA-10666 and CA-11502 from the National Cancer Institute.