Two types of lethal damage induced by pepleomycin in cultured Chinese hamster V79 cells

The cytotoxic effect of pepleomycin (PEP), a derivative of bleomycin (BLM), was investigated and compared with that of BLM on cultured Chinese hamster V79 cells. The concentration-response curve of PEP was biphasic, like that of BLM: the D0 values of the first and second slopes for PEP were 32 micrograms/ml and 140 micrograms/ml, while those of BLM were 60 micrograms/ml and 140 micrograms/ml, respectively. The ratios of D0 for BLM to that for PEP were 1.88 for the first slope and 1.0 for the second one, suggesting that PEP is more cytotoxic than BLM on a unit concentration basis. The time-response curve for PEP showed that the surviving fraction dropped immediately, then rose gradually and finally declined slowly. Analysis of these curves together with the results of further experiments suggested the induction of two types of lethal damage by PEP; potentially lethal damage and non-reparable lethal damage. Potentially lethal damage was induced by PEP treatment, developed within a few minutes, was fixed as lethal damage by trypsinization and was repaired fully within 1 hr if trypsinization was not applied. Non-reparable lethal damage was another type of damage induced by PEP and led to cell death without repair. The two types of lethal damage can account for not only the various shapes of survival curves, but also the differences in cytotoxicity of PEP and BLM.