Darroudi F, Natarajan A T
Mutat Res. 1987 Mar;177(1):149-60. doi: 10.1016/0027-5107(87)90030-3.
The cell killing and induction of sister-chromatid exchanges (SCEs) by X-rays and short-wave ultraviolet (UV) irradiation in combination with inhibitors of DNA repair, 3-aminobenzamide (3AB), cytosine arabinoside (ara-C) or aphidicolin (APC) were studied in wild-type CHO-K1 and two X-ray-sensitive mutants, xrs 5 and xrs 6 cells. The spontaneous frequency of SCEs was similar in the mutants and the wild-type CHO-K1 cells (8.4-10.3 SCEs/cell). Though X-rays are known to be poor inducers of SCEs, a dose-dependent increase in the frequency of SCEs in xrs 6 cells (doubling at 150 rad) was found in comparison to a small increase in xrs 5 and no increase in wild-type CHO-K1 cells. 3AB, an inhibitor of poly(ADP-ribose) synthetase increased the spontaneous frequency of SCEs in all the cell types. 3AB did not potentiate the X-ray-induced frequency of SCEs in any of the cell lines. Ara-C, an inhibitor of DNA polymerase alpha, increased the frequency of SCEs in all the cell lines. In combined treatment with X-rays, ara-C had no synergistic effect in xrs 5 and xrs 6 cells, but the frequency of SCEs increased in X-irradiated wild-type CHO-K1 cells post-treated with ara-C. For the induced frequency of SCEs, CHO-K1 cells treated with X-rays plus ara-C behaved like xrs 6 cells treated with X-rays alone, suggesting a possible defect in DNA base damage repair in xrs 6 cells, in addition to the known defective repair of DNA double-strand breaks (DSBs). Survival experiments revealed higher sensitivity of xrs 5 and xrs 6 mutant cells to the cell killing effect of X-rays in S-phase when compared to wild-type CHO-K1 cells. The mutants responded with lesser sensitivity to cell killing effect of ara-C and APC than CHO-K1 cells, the relative sensitivity to ara-C or APC being CHO-K1 greater than xrs 5 greater than xrs 6 cells. When X-irradiation was coupled with ara-C, the results obtained for survival were similar to those of the SCE test, i.e., unlike wild-type CHO-K1, no synergistic effect was observed in xrs 5 or xrs 6 cells. After UV-irradiation, the frequency of SCEs increased similarly in wild-type CHO-K1 and xrs 6 cells, but xrs 5 cells responded with lower frequency of SCEs.(ABSTRACT TRUNCATED AT 400 WORDS)
研究了X射线和短波紫外线（UV）照射联合DNA修复抑制剂3-氨基苯甲酰胺（3AB）、阿糖胞苷（ara-C）或阿非迪霉素（APC）对野生型CHO-K1细胞以及两个X射线敏感突变体xrs 5和xrs 6细胞的细胞杀伤作用和姐妹染色单体交换（SCE）诱导情况。突变体和野生型CHO-K1细胞中SCE的自发频率相似（8.4 - 10.3次SCE/细胞）。尽管已知X射线诱导SCE的能力较弱，但与xrs 5细胞中少量增加以及野生型CHO-K1细胞中无增加相比，发现xrs 6细胞中SCE频率呈剂量依赖性增加（在150拉德时翻倍）。3AB是聚（ADP - 核糖）合成酶的抑制剂，可增加所有细胞类型中SCE的自发频率。3AB在任何细胞系中均未增强X射线诱导的SCE频率。ara-C是DNA聚合酶α的抑制剂，可增加所有细胞系中SCE的频率。在与X射线联合处理时，ara-C在xrs 5和xrs 6细胞中无协同作用，但在X射线照射后的野生型CHO-K1细胞中，用ara-C后处理，SCE频率增加。对于诱导的SCE频率，用X射线加ara-C处理的CHO-K1细胞表现得与单独用X射线处理的xrs 6细胞相似，这表明除了已知的DNA双链断裂（DSB）修复缺陷外，xrs 6细胞在DNA碱基损伤修复方面可能存在缺陷。存活实验表明，与野生型CHO-K1细胞相比，xrs 5和xrs 6突变细胞在S期对X射线的细胞杀伤作用更敏感。突变体对ara-C和APC的细胞杀伤作用的敏感性低于CHO-K1细胞，对ara-C或APC的相对敏感性为CHO-K1大于xrs 5大于xrs 6细胞。当X射线与ara-C联合时，存活实验结果与SCE测试结果相似，即与野生型CHO-K1不同，xrs 5或xrs 6细胞中未观察到协同作用。紫外线照射后，野生型CHO-K1细胞和xrs 6细胞中SCE频率的增加相似，但xrs 5细胞中SCE频率的增加较低。（摘要截短于400字）
