Lethal and cytokinetic effects of mitomycin C on cultured human colon cancer cells.
Lethal and cytokinetic effects of mitomycin C on cultured human colon cancer cells.
复制标题
丝裂霉素 C 对培养的人结肠癌细胞的致死和细胞因子作用。
作者：
B. Barlogie;B. Drewinko
采用集落形成法检测细胞存活率，DNA流式细胞仪检测细胞周期扰动，评价丝裂霉素C(MC)对体外培养的人结肠腺癌(LoVo)细胞的致死性和细胞动力学效应。在指数生长期和稳定期(DQ=0.4微克/毫升；DO=1.0微克/毫升)，MC诱发阈值-指数型1小时-剂量依赖生存曲线。在指数生长的培养中，给定的MC暴露剂量会产生等毒效应，而不考虑不间断处理所使用的特定药物浓度和暴露时间。然而，剂量分割实验显示，LoVo细胞有能力部分修复MC暴露造成的亚致死性损伤。5微克/毫升MC作用24小时后，G2、S、G1期细胞周期呈可逆性延迟或阻断，呈冰冻周期分布。S期细胞周期可逆性延迟，但未出现明显的G2期阻滞，可用于S期特异性药物的应用，以最大限度地杀伤细胞。
The lethal and cytokinetic effects of mitomycin C (MC) as a function of drug concentration and exposure time were assessed in cultured human colon adenocarcinoma (LoVo) cells using colony formation to determine cell survival and DNA flow cytometry to examine cell cycle perturbation. MC evoked threshold-exponential type 1-hr dose-dependent survival curves in both exponential and stationary growth phases (Dq = 0.4 microgram/ml; Do = 1.0 microgram/ml). In exponentially growing cultures, a given exposure dose of MC induced equitoxic effects regardless of the specific drug concentration and exposure time used with uninterrupted treatment. However, dose fractionation experiments revealed the ability of LoVo cells to partially repair sublethal damage from MC exposure. Cell cycle progression was reversibly delayed or blocked in G2, S, and G1 phases in this order of sensitivity, with a frozen cycle distribution after greater than or equal to 24 hr treatment with 5 microgram of MC per ml. The reversible delay in S-phase traverse without a significant subsequent G2 block may be exploitable for administration of S-phase-specific drugs to maximize cell kill.