Morgan W F, Wolff S
Cytogenet Cell Genet. 1984;38(1):34-8. doi: 10.1159/000132026.
The poly(ADP-ribose) polymerase inhibitor, 3-aminobenzamide (3AB), significantly increases sister chromatid exchange (SCE) frequency without causing apparent damage to cellular DNA. A previous study has suggested that the increase of SCEs by 3AB results from DNA replication on a template strand containing bromodeoxyuridine (BrdU), which is used to visualize SCEs. Therefore, to study the importance of BrdU incorporation on the induction of SCEs by 3AB, we analyzed exchanges induced during the first round of replication (twin SCEs) and those induced during the second (single SCEs). 3AB increased the formation of SCEs in both replication cycles, but significantly more exchanges were induced in the second cycle, when BrdU was present in the template DNA. These data are consistent with the suggestion that the presence of BrdU in the template strand of DNA plays an important role in SCE induction by 3AB. However, we also studied 3AB-induced SCEs by autoradiography of cells cultured with 3H-thymidine (3H-dT) instead of BrdU. A significant increase in SCE frequency was also observed in cells from these cultures. Furthermore, the analysis of twin and single SCEs showed that with 3H-dT too, there was a greater increase in SCEs in the second cycle than in the first. Thus, SCE induction by 3AB in the second cycle is not dependent on the presence of BrdU in template DNA. Incubation of cells with deoxycytidine was found to have no effect on the frequency of SCEs induced by 3AB, suggesting that an imbalance in the deoxycytidine precursor pool did not account for the effect.
聚(ADP - 核糖)聚合酶抑制剂3 - 氨基苯甲酰胺(3AB)可显著增加姐妹染色单体交换(SCE)频率,而不会对细胞DNA造成明显损伤。先前的一项研究表明,3AB导致SCE增加是由于在含有用于可视化SCE的溴脱氧尿苷(BrdU)的模板链上进行DNA复制。因此,为了研究BrdU掺入对3AB诱导SCE的重要性,我们分析了第一轮复制期间诱导的交换(双SCE)和第二轮复制期间诱导的交换(单SCE)。3AB在两个复制周期中均增加了SCE的形成,但当模板DNA中存在BrdU时,第二轮诱导的交换明显更多。这些数据与DNA模板链中BrdU的存在在3AB诱导SCE中起重要作用的观点一致。然而,我们还用3H - 胸苷(3H - dT)代替BrdU培养细胞进行放射自显影来研究3AB诱导的SCE。在这些培养的细胞中也观察到SCE频率显著增加。此外,对双SCE和单SCE的分析表明,使用3H - dT时,第二轮SCE的增加也比第一轮更大。因此,3AB在第二轮诱导SCE不依赖于模板DNA中BrdU的存在。发现用脱氧胞苷孵育细胞对3AB诱导的SCE频率没有影响,这表明脱氧胞苷前体池的失衡不能解释这种效应。