Stopper H, Pechan R, Schiffmann D
Institute of Pharmacology and Toxicology, University of Würzburg, Germany.
Mutat Res. 1992 Sep;283(1):21-8. doi: 10.1016/0165-7992(92)90117-z.
It is known that 5-azacytidine (5-AC) induces tumors in several organs of rats and mice. The mechanisms of these effects are still poorly understood although it is known that 5-AC can be incorporated into DNA. Furthermore, it can inhibit DNA methylation. The known data on its clastogenic and/or gene mutation-inducing potential are still controversial. Therefore, we have investigated the kinds of genotoxic effects caused by 5-AC in Syrian hamster embryo (SHE) fibroblasts. Three different endpoints (micronucleus formation, unscheduled DNA synthesis (UDS) and cell transformation) were assayed under similar conditions of metabolism and dose at target in this cell system. 5-AC induces morphological transformation of SHE cells, but not UDS. Therefore, 5-AC does not seem to cause repairable DNA lesions. Furthermore, our studies revealed that 5-AC is a potent inducer of micronuclei in the SHE system. Immunocytochemical analysis revealed that a certain percentage of these contain kinetochores indicating that 5-AC may induce both clastogenic events and numerical chromosome changes.
已知5-氮杂胞苷（5-AC）可在大鼠和小鼠的多个器官中诱发肿瘤。尽管已知5-AC可掺入DNA，但其这些作用的机制仍了解甚少。此外，它可抑制DNA甲基化。关于其致断裂和/或诱导基因突变潜力的已知数据仍存在争议。因此，我们研究了5-AC在叙利亚仓鼠胚胎（SHE）成纤维细胞中引起的遗传毒性效应类型。在该细胞系统中，在相似的代谢条件和靶剂量下，检测了三个不同的终点（微核形成、非程序性DNA合成（UDS）和细胞转化）。5-AC可诱导SHE细胞发生形态转化，但不能诱导UDS。因此，5-AC似乎不会引起可修复的DNA损伤。此外，我们的研究表明，5-AC是SHE系统中微核的有效诱导剂。免疫细胞化学分析显示，其中一定比例含有动粒，表明5-AC可能既诱导断裂事件，也诱导染色体数目变化。
