Saito T, Kamata R, Okada S
Gan. 1984 Feb;75(2):143-50.
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.
研究了博来霉素（BLM）的衍生物培普利欧霉素（PEP）对培养的中国仓鼠V79细胞的细胞毒性作用，并与BLM进行了比较。PEP的浓度-反应曲线呈双相，与BLM的相似：PEP第一和第二斜率的D0值分别为32微克/毫升和140微克/毫升，而BLM的分别为60微克/毫升和140微克/毫升。BLM与PEP的D0比值，第一斜率为1.88，第二斜率为1.0，这表明在单位浓度基础上，PEP比BLM具有更强的细胞毒性。PEP的时间-反应曲线显示，存活分数立即下降，然后逐渐上升，最后缓慢下降。对这些曲线的分析以及进一步实验的结果表明，PEP可诱导两种类型的致死性损伤；潜在致死性损伤和不可修复的致死性损伤。潜在致死性损伤由PEP处理诱导，在几分钟内形成，通过胰蛋白酶消化固定为致死性损伤，如果不进行胰蛋白酶消化，则在1小时内可完全修复。不可修复的致死性损伤是PEP诱导的另一种损伤，导致细胞死亡且无法修复。这两种类型的致死性损伤不仅可以解释存活曲线的各种形状，还可以解释PEP和BLM细胞毒性的差异。
