A new mechanism of mammalian cell resistance to the toxic effects of DNA-binding agents

被引:1
|
作者
Levina, V [1 ]
Varfolomeeva, E [1 ]
Sukhareva, E [1 ]
Shabalina, E [1 ]
Drobchenko, E [1 ]
Filatov, M [1 ]
机构
[1] Petersburg Nucl Phys Inst, St Petersburg 188350, Russia
来源
ATLA-ALTERNATIVES TO LABORATORY ANIMALS | 2000年 / 28卷 / 03期
关键词
multidrug resistance; DNA clearing; mammalian cells; Hoechst; 33342; mitomycin C;
D O I
10.1177/026119290002800308
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The phenomenon of active dissociation of the noncovalently binding vital dye Hoechst 33342 from DNA in living cells (DNA clearing) is described. Step-by-step selection with increasing concentrations of the dye resulted in a series of rodent cell lines that were resistant to the toxic action of Hoechst 33342. Some of the lines exhibited enhanced dissociation of the bisbenzimidazole dye-DNA complex. Two cell lines from this group (AA8HoeR-7 and LHoeR-3) were analysed in detail and compared with a Syrian hamster tumour cell line, a typical example of mdr-I-mediated multidrug-resistant cell lines. The markedly enhanced level of DNA clearing in AA8HoeR-7 and LHoeR-3 cells leads to high cellular resistance to the toxic effect of Hoechst 33343 and cross-resistance to mitomycin C, a minor-groove alkylating agent in clinical use. Our results suggest that DNA clearing is one of the mechanisms of multidrug resistance in tumour cells.
引用
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页码:451 / 456
页数:6
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