Nakagawa S, Nakamura N, Fujioka M, Mori C
Department of Anatomy and Developmental Biology, Faculty of Medicine, Kyoto University, Japan.
Toxicol Appl Pharmacol. 1997 Dec;147(2):204-13. doi: 10.1006/taap.1997.8246.
Spermatogenic cell degeneration in the mature mammalian testis occurs both spontaneously during normal spermatogenesis and in response to cytotoxic agents. Mitomycin C (MC) is an antibiotic that affects DNA synthesis. In the present study, we examined the induction of mouse spermatogenic cell apoptosis by MC, using TdT-mediated dUTP-biotin nick end labeling (TUNEL) to detect high levels of DNA fragmentation in situ, transmission electron microscopy (TEM) to observe nuclear chromatin condensation, and molecular methods to detect DNA ladders. This study shows that in the testis of MC-treated mice: (i) apoptotic cell death with fragmentation of nuclear DNA is induced by MC dose-dependently, (ii) apoptotic cell death is most commonly found in the spermatogonia and less frequently in spermatocytes, and (iii) apoptotic cell death induced by MC is not specific for the seminiferous stage of the tubules. The present study suggests that the spermatogenic cell apoptosis induced by MC might be involved in its testicular toxicity.
成熟哺乳动物睾丸中的生精细胞退化在正常精子发生过程中会自发出现,也会因细胞毒性药物而发生。丝裂霉素C(MC)是一种影响DNA合成的抗生素。在本研究中,我们使用TdT介导的dUTP生物素缺口末端标记法(TUNEL)原位检测高水平的DNA片段化、透射电子显微镜(TEM)观察核染色质凝聚以及分子方法检测DNA梯带,来研究MC对小鼠生精细胞凋亡的诱导作用。本研究表明,在经MC处理的小鼠睾丸中:(i)MC剂量依赖性地诱导核DNA片段化的凋亡细胞死亡;(ii)凋亡细胞死亡最常见于精原细胞,较少见于精母细胞;(iii)MC诱导的凋亡细胞死亡对曲细精管的生精阶段不具有特异性。本研究提示,MC诱导的生精细胞凋亡可能与其睾丸毒性有关。