Stopper H, Kirchner S, Schiffmann D, Poot M
Institute of Pharmacology and Toxicology, University of Würzburg, Germany.
Pathobiology. 1994;62(4):180-5. doi: 10.1159/000163908.
In addition to its tumor-promoting activity in hormone-receptive tissue, the carcinogenic estrogen diethylstilbestrol (DES) has been found to induce cell transformation, aneuploidy and micronucleus formation in mammalian cells. The majority of these micronuclei contained whole chromosomes and were formed during mitosis. Here a possible relationship between a disturbance in cell cycle progression and micronucleus formation is investigated by exposing Syrian hamster embryo (SHE) cells to DES. Continuous bromodeoxyuridine labeling followed by bivariate Hoechst 33258/ethidium bromide flow cytometry was employed for analysis of cell cycle transit and related to the time course of micronucleus formation. Treatment of SHE cells with DES resulted in delayed and impaired cell activation (exit from the G0/G1 phase), impaired S-phase transit and, mainly, G2-phase traverse. Cells forming micronuclei, on the other hand, were predominantly in G2 phase during DES treatment. These results suggest that impairment of S and G2 transit may involve a process ultimately leading to micronucleus formation.
除了在激素敏感组织中的促肿瘤活性外，致癌雌激素己烯雌酚（DES）还被发现可诱导哺乳动物细胞发生细胞转化、非整倍体和微核形成。这些微核大多包含整条染色体，且在有丝分裂期间形成。在此，通过将叙利亚仓鼠胚胎（SHE）细胞暴露于DES，研究细胞周期进程紊乱与微核形成之间的可能关系。采用连续溴脱氧尿苷标记，随后进行双变量Hoechst 33258/溴化乙锭流式细胞术分析细胞周期进程，并与微核形成的时间进程相关联。用DES处理SHE细胞导致细胞活化延迟且受损（退出G0/G1期）、S期进程受损，主要是G2期进程受损。另一方面，在DES处理期间，形成微核的细胞主要处于G2期。这些结果表明，S期和G2期进程的受损可能涉及一个最终导致微核形成的过程。
