Gantt R, Parshad R, Price F M, Sanford K K
Radiat Res. 1986 Nov;108(2):117-26.
Human tumor cells and cells from cancer-prone individuals, compared with those from normal individuals, show a significantly higher incidence of chromatid breaks and gaps seen in metaphase cells immediately after G2 X irradiation. Previous studies with DNA repair-deficient mutants and DNA repair inhibitors strongly indicate that the enhancement results from a G2 deficiency(ies) in DNA repair. We report here biochemical evidence for a DNA repair deficiency that correlates with the cytogenetic studies. In the alkaline elution technique, after a pulse label with radioactive thymidine in the presence of 3-acetylaminobenzamide (a G2-phase blocker) and X irradiation, DNA from tumor or cancer-prone cells elutes more rapidly during the postirradiation period than that from normal cells. These results indicate that the DNA of tumor and cancer-prone cells either repairs more slowly or acquires more breaks than that of normal cells; breaks can accumulate during incomplete or deficient repair processes. The kinetic difference between normal and tumor or cancer-prone cells in DNA strand-break repair reaches a maximum within 2 h, and this maximum corresponds to the kinetic difference in chromatid aberration incidence following X irradiation reported previously. These findings support the concept that cells showing enhanced G2 chromatid radiosensitivity are deficient in DNA repair. The findings could also lead to a biochemical assay for cancer susceptibility.
与正常个体的细胞相比，人类肿瘤细胞以及癌症易感个体的细胞在G2期X射线照射后，中期细胞中染色单体断裂和裂隙的发生率显著更高。先前对DNA修复缺陷突变体和DNA修复抑制剂的研究有力地表明，这种增强是由DNA修复中的G2缺陷导致的。我们在此报告与细胞遗传学研究相关的DNA修复缺陷的生化证据。在碱性洗脱技术中，在存在3-乙酰氨基苯甲酰胺（一种G2期阻滞剂）的情况下用放射性胸苷进行脉冲标记并进行X射线照射后，肿瘤或癌症易感细胞的DNA在照射后洗脱得比正常细胞更快。这些结果表明，肿瘤和癌症易感细胞的DNA修复速度较慢或比正常细胞获得更多的断裂；断裂可在不完全或缺陷的修复过程中积累。正常细胞与肿瘤或癌症易感细胞在DNA链断裂修复方面的动力学差异在2小时内达到最大值，且该最大值与先前报道的X射线照射后染色单体畸变发生率的动力学差异相对应。这些发现支持了这样的概念，即显示出增强的G2染色单体放射敏感性的细胞存在DNA修复缺陷。这些发现还可能导致一种用于癌症易感性的生化检测方法。
