Okada M, Goto M, Furuichi Y, Sugimoto M
AGENE Research Institute, Kamakura, Kanagawa, Japan.
Biol Pharm Bull. 1998 Mar;21(3):235-9. doi: 10.1248/bpb.21.235.
We studied the effects of nine cytotoxic drugs on three groups of B-lymphoblastoid cell lines transformed by Epstein-Barr virus (EBV): group 1, mortal cell lines from normal individuals; group 2, immortalized cell lines from normal individuals with strong telomerase activity; group 3, mortal cell lines from Werner's syndrome (WS) patients. Aminoglycoside antibiotics and alkylating drugs showed significantly stronger cytotoxic effects on immortalized cell lines than on mortal cell lines or the cell lines before immortalization. In contrast, topoisomerase II inhibitors showed no difference or they tended to be less cytotoxic to immortalized cell lines. Mortal cell lines from normal individuals and WS patients showed no difference in sensitivity against all the drugs examined except for the topoisomerase I inhibitor, camptothecin, which had a stronger cytotoxic effect on WS cell lines than other cell lines. We discuss the mechanisms underlying these cytotoxic effects.
我们研究了九种细胞毒性药物对三组由爱泼斯坦-巴尔病毒（EBV）转化的B淋巴母细胞系的影响：第1组，来自正常个体的有限传代细胞系；第2组，来自具有强端粒酶活性的正常个体的永生化细胞系；第3组，来自沃纳综合征（WS）患者的有限传代细胞系。氨基糖苷类抗生素和烷化剂对永生化细胞系的细胞毒性作用明显强于对有限传代细胞系或永生化前的细胞系。相比之下，拓扑异构酶II抑制剂没有差异，或者它们对永生化细胞系的细胞毒性倾向于较小。来自正常个体和WS患者的有限传代细胞系对所有检测药物的敏感性没有差异，除了拓扑异构酶I抑制剂喜树碱，它对WS细胞系的细胞毒性作用比其他细胞系更强。我们讨论了这些细胞毒性作用的潜在机制。
