Ritch P S, Occhipinti S J, Skramstad K S, Shackney S E
Cancer Treat Rep. 1982 May;66(5):1159-68.
Doxorubicin (ADR) lethality was studied in Sarcoma 180 cells grown in vitro during log phase and early plateau phase. For both log phase and plateau phase cells, ADR lethality increased progressively with continuous drug exposure, and was dependent on drug concentration at every point in time. For any given level of toxicity to log phase cells, greater killing of plateau phase cells was achieved with prolonged drug exposure. The inhibition of DNA synthesis by ADR was delayed in onset, and increased gradually, both at low and high drug concentrations. The data suggest that the dependence of ADR lethality on proliferation rate and the higher therapeutic ratio in plateau phase cells with prolonged drug exposure are not directly related to the ADR effects on DNA synthesis.
在体外对数期和早期平台期生长的肉瘤180细胞中研究了阿霉素（ADR）的致死性。对于对数期和平台期细胞，随着持续药物暴露，ADR致死性逐渐增加，并且在每个时间点都依赖于药物浓度。对于任何给定的对数期细胞毒性水平，延长药物暴露可实现对平台期细胞更强的杀伤。ADR对DNA合成的抑制作用起效延迟，且在低药物浓度和高药物浓度下均逐渐增加。数据表明，ADR致死性对增殖率的依赖性以及延长药物暴露时平台期细胞中更高的治疗指数与ADR对DNA合成的影响没有直接关系。
