Di Leonardo A, Maddalena A, Cavolina P
Dipartimento di Biologia Cellulare e dello Sviluppo A. Monroy, University of Palermo, Italy.
Mutat Res. 1992 Oct;269(2):319-27. doi: 10.1016/0027-5107(92)90214-m.
Spontaneously nalidixic acid-resistant lines (NAr lines) were selected from a V79 Chinese hamster cell line and phenotypically characterized. NAr lines showed an increased doubling time, a higher number of spontaneous SCE, and more interestingly, decreased DNA topoisomerase II activity. These lines were also cross-resistant to the eukaryotic topoisomerase II inhibitors etoposide and adriamycin, but showed the same level of sensitivity as the parental line to the DNA topoisomerase I inhibitor camptothecin. NAr lines were cross-resistant to other drugs, such as PALA, MTX and MPA, resistance to which has been shown to arise by amplification of the target genes. This last feature, together with enhanced cross-resistance to PALA and MTX when employed simultaneously, suggests that NAr lines have an 'amplification prone' phenotype. From these results the decreased activity of topoisomerase II seems to be involved in the generation of amplified sequences possibly by affecting recombinational events underlying gene amplification.
从V79中国仓鼠细胞系中筛选出自发耐萘啶酸的细胞系（NAr细胞系）并对其进行表型特征分析。NAr细胞系显示出倍增时间延长、自发姐妹染色单体交换次数增多，更有趣的是，DNA拓扑异构酶II活性降低。这些细胞系对真核拓扑异构酶II抑制剂依托泊苷和阿霉素也具有交叉抗性，但对DNA拓扑异构酶I抑制剂喜树碱的敏感性与亲代细胞系相同。NAr细胞系对其他药物如N-磷乙酰-L-天冬氨酸（PALA）、甲氨蝶呤（MTX）和霉酚酸（MPA）也具有交叉抗性，对这些药物的抗性已证明是由靶基因扩增引起的。最后这一特征，以及同时使用时对PALA和MTX增强的交叉抗性，表明NAr细胞系具有“易于扩增”的表型。从这些结果来看，拓扑异构酶II活性降低似乎参与了扩增序列的产生，可能是通过影响基因扩增背后的重组事件来实现的。
