Enhanced radiation-induced cell killing by carboplatin in cells of repair-proficient and repair-deficient cell lines.
Enhanced radiation-induced cell killing by carboplatin in cells of repair-proficient and repair-deficient cell lines.
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DOI：
10.2307/3579263
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发表时间：
1995-11
影响因子：
3.4
通讯作者：
Li-xi Yang;Evan B. Douple;Julia A. O'Hara;Robin A. Crabtree;Alan Eastman
中科院分区：
文献类型：
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作者：
Li-xi Yang;Evan B. Douple;Julia A. O'Hara;Robin A. Crabtree;Alan Eastman
本研究的目的是确定两种修复过程中任何一种的缺陷是否会影响卡铂增强辐射诱导细胞杀伤的现象，这种现象先前已在一种细胞系（V79）中报道过，并且可能是这两种治疗方式之间相互作用的结果。当四种细胞系的细胞在空气或缺氧的照射前和照射期间接触卡铂时，细胞杀伤作用增强。在精通切除修复和 DNA 双链断裂修复的细胞系（K1 和 AA8）中，以及在核苷酸切除修复缺陷的细胞系（UV41）中，增强的特征是生存曲线肩部区域的减少（由 Dq 的减少表示）和生存曲线末端区域 D0 的减少（针对暴露在空气和缺氧条件下的细胞确定）。在 DNA 双链断裂修复缺陷的细胞系 (xrs-5) 中仅观察到后一种效应。使用修复饱和模型和 N. Albright 开发的计算机程序（Radiat. Res. 118, 112-130, 1989）将生存曲线拟合到数据。在缺氧情况下，K1、AA8 和 UV41 细胞的 Dq 降低幅度分别为 7.0 Gy 至 2.1 Gy、3.3 Gy 至 0 Gy 和 1.7 Gy 至 0 Gy。敏化剂增强比率范围为 1.3 至 1.7，并且与空气中和缺氧条件下的照射相似。卡铂与辐射结合增强的细胞杀伤作用需要药物水平足以单独通过药物产生细胞毒性，如 UV41 细胞系所示，该细胞系本质上对卡铂敏感，其中其他细胞系所需药物浓度的 1/30 在仅 5 µM 的等毒剂量下产生增强的细胞杀伤作用。
The objective of this study was to determine whether a deficiency for either one of two repair processes influences the phenomenon of enhancement of radiation-induced cell killing by carboplatin which has been reported previously in one cell line (V79) and which is presumably a result of an interaction between these two therapeutic modalities. Cell killing was enhanced in cells of four cell lines when the cells were exposed to carboplatin before and during irradiation in either air or hypoxia. In cell lines proficient in both excision repair and DNA double-strand break repair (K1 and AA8), and in a cell line deficient in nucleotide excision repair (UV41), the enhancement was characterized as both a reduction in the shoulder region of the survival curves indicated by a reduced Dq and a reduction in D0 in the terminal region of the survival curves determined for cells exposed in air and under hypoxic conditions. Only the latter effect was observed in a cell line deficient in DNA double-strand break repair (xrs-5). The survival curves were fitted to the data using the repair saturation model and a computer program developed by N. Albright (Radiat. Res. 118, 112-130, 1989). In hypoxia, the reductions in Dq were as great as from 7.0 Gy to 2.1 Gy, 3.3 Gy to 0 Gy and 1.7 Gy to 0 Gy for K1, AA8 and UV41 cells, respectively. Sensitizer enhancement ratios ranged from 1.3 to 1.7 and were similar for irradiation in air and under hypoxic conditions. This enhanced cell killing by carboplatin combined with radiation required levels of the drug sufficient to produce cytotoxicity by the drug alone as exemplified by the UV41 cell line, which is intrinsically sensitive to carboplatin and in which 1/30 of the drug concentration required for the other cell lines produced an enhanced cell killing at an equitoxic dose of only 5 microM.