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

页码：451 / 456

页数：6