Zhao J H, Tohda H, Oikawa A
Research Institute for Tuberculosis and Cancer, Tohoku University, Sendai, Japan.
Mutat Res. 1992 May;282(1):49-54. doi: 10.1016/0165-7992(92)90073-q.
Camptothecin (CPT), a DNA topoisomerase I inhibitor, dose-dependently induced sister-chromatid exchanges (SCEs) in human lymphoblastoid cells NL3 when added with bromodeoxyuridine (BrdUrd) for 2 cell cycles. CPT given prior to the addition of BrdUrd scarcely induced SCEs. When cells with BrdUrd present for 2 cell cycles were treated with CPT in the first cell cycle, the SCE induction was evident, though its frequency was considerably lower than in cells treated in the second cell cycle, indicating that BrdUrd is essential for SCE induction by CPT. The replacement of BrdUrd with thymidine in the second cell cycle gave the same results in SCE induction and its removal without replacement resulted in a reduced but still clear induction by CPT treatment in the second cell cycle. These results indicate that BrdUrd, not only incorporated into DNA but also in the culture medium, plays an essential role in SCE induction by CPT. CPT treatment in the G1 phase of the second cell cycle also induced SCEs, as did treatment in the S phase. In phytohemagglutinin-stimulated peripheral lymphocytes, CPT given in the G1 phase of the second cell cycle, but not of the first one, also induced SCEs though to a lesser degree. These findings suggest that CPT is capable of inducing DNA lesions during the G1 phase when chromosomes contain BrdUrd-substituted DNA. The lesions are presumably formed in connection with transcription, which requires topoisomerase I activity, and are believed to be long-lived enough to induce SCEs in the following S phase.
喜树碱（CPT）是一种DNA拓扑异构酶I抑制剂，当与溴脱氧尿苷（BrdUrd）一起添加2个细胞周期时，它能在人淋巴母细胞系NL3中剂量依赖性地诱导姐妹染色单体交换（SCEs）。在添加BrdUrd之前给予CPT几乎不会诱导SCEs。当在第一个细胞周期中用CPT处理存在BrdUrd 2个细胞周期的细胞时，SCE诱导是明显的，尽管其频率远低于在第二个细胞周期中处理的细胞，这表明BrdUrd对于CPT诱导SCEs是必不可少的。在第二个细胞周期中用胸苷替代BrdUrd在SCE诱导方面产生相同的结果，并且在没有替代的情况下去除它导致在第二个细胞周期中CPT处理诱导的SCE减少但仍然明显。这些结果表明，BrdUrd不仅掺入DNA中，而且在培养基中，在CPT诱导SCEs中起重要作用。在第二个细胞周期的G1期进行CPT处理也能诱导SCEs，在S期处理也是如此。在植物血凝素刺激的外周淋巴细胞中，在第二个细胞周期的G1期给予CPT（但不是第一个细胞周期）也能诱导SCEs，尽管程度较小。这些发现表明，当染色体含有BrdUrd替代的DNA时，CPT能够在G1期诱导DNA损伤。这些损伤可能与转录有关，转录需要拓扑异构酶I的活性，并且被认为寿命足够长，能够在随后的S期诱导SCEs。
