Sailaja G, Nayak R, Antony A
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India.
Biochem Pharmacol. 1996 Sep 27;52(6):857-62. doi: 10.1016/0006-2952(96)82183-6.
Azidothymidine (AZT), which has been extensively used as an antiviral agent in the treatment of AIDS, showed strong inhibition of growth of Sp2/0 cells in vitro. AZT-treated cells showed a decrease in viability in a dose-dependent manner. AZT specifically induced typical apoptotic cell death with DNA double-strand cleavage and subsequent formation of apoptotic bodies. The induction of DNA double-strand cleavage into the oligonucleosomal ladder by AZT was protected in the presence of thymidine or uridine. An increase in endonuclease activity from nuclear extract of AZT-treated cells was observed. The enzyme activity was found to be Ca(2+)-and Mg(2+)-dependent and was inhibited by zinc acetate. A marked enhancement of PARP activity was observed in AZT-treated cells. These observations show that AZT can trigger both morphological and biochemical changes typical of apoptosis in the mouse myeloma cell line Sp2/0.
叠氮胸苷（AZT）已被广泛用作治疗艾滋病的抗病毒药物，在体外对Sp2/0细胞的生长表现出强烈抑制作用。经AZT处理的细胞活力呈剂量依赖性下降。AZT特异性诱导典型的凋亡性细胞死亡，伴有DNA双链断裂及随后凋亡小体的形成。在胸苷或尿苷存在的情况下，AZT诱导的DNA双链断裂形成寡核小体梯状条带受到保护。观察到经AZT处理的细胞的核提取物中的核酸内切酶活性增加。发现该酶活性依赖于Ca(2+)和Mg(2+)，并被醋酸锌抑制。在经AZT处理的细胞中观察到聚（ADP-核糖）聚合酶（PARP）活性显著增强。这些观察结果表明，AZT可引发小鼠骨髓瘤细胞系Sp2/0中典型的凋亡形态学和生化变化。
