Bill C A, Mendoza E A, Vrdoljak E, Tofilon P J
Department of Experimental Radiotherapy, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Radiother Oncol. 1993 Jul;28(1):63-8. doi: 10.1016/0167-8140(93)90187-d.
Aclacinomycin A (ACM), a potent inducer of leukemic cell differentiation, significantly enhances the radiosensitivity of a human colon tumor cell line (Clone A) when cultures are exposed to 15-nM concentrations for 3 days before irradiation. We now demonstrate that incubation with ACM after irradiation can also enhance Clone A cell killing. The maximum increase in cell killing, based on colony-forming ability, occurred when Clone A cells were exposed for 1 h to 5 microM ACM added 1 or 2 h after irradiation. The post-irradiation ACM protocol reduced the terminal slope (as reflected by D0) of the radiation cell survival curve with no change in the low-dose, shoulder region of the curve (Dq value). In contrast, for pre-irradiation treatment with ACM (15 nM, 3 days), the shoulder region of the curve was reduced with no change in the terminal slope. For pre- and post-irradiation ACM treatment the dose enhancement factors at 0.10 survival were 1.22 and 1.28, respectively. When ACM was given both before and after irradiation both the shoulder and terminal slope values decreased to produce a dose enhancement factor at a surviving fraction of 0.10 of 1.50. These data suggest that the enhanced cell killing produced by pre- and post-irradiation treatment with ACM is achieved through different mechanisms.
阿克拉霉素A（ACM）是一种有效的白血病细胞分化诱导剂，当在照射前3天将培养物暴露于15 nM浓度时，它能显著增强人结肠肿瘤细胞系（克隆A）的放射敏感性。我们现在证明，照射后用ACM孵育也能增强克隆A细胞的杀伤作用。基于集落形成能力，当克隆A细胞在照射后1或2小时暴露于5 microM ACM 1小时时，细胞杀伤作用达到最大增加。照射后ACM方案降低了放射细胞存活曲线的终末斜率（由D0反映），而曲线的低剂量肩部区域（Dq值）没有变化。相比之下，对于照射前用ACM（15 nM，3天）处理，曲线的肩部区域减小，终末斜率没有变化。对于照射前和照射后ACM处理，0.10存活时的剂量增强因子分别为1.22和1.28。当在照射前后都给予ACM时，肩部和终末斜率值均降低，在存活分数为0.10时产生的剂量增强因子为1.50。这些数据表明，照射前和照射后用ACM处理产生的增强的细胞杀伤作用是通过不同机制实现的。
