A new mechanism of mammalian cell resistance to the toxic effects of DNA-binding agents
被引:1
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作者:
Levina, V
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h-index: 0
机构:
Petersburg Nucl Phys Inst, St Petersburg 188350, RussiaPetersburg Nucl Phys Inst, St Petersburg 188350, Russia
Levina, V
[1
]
Varfolomeeva, E
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h-index: 0
机构:
Petersburg Nucl Phys Inst, St Petersburg 188350, RussiaPetersburg Nucl Phys Inst, St Petersburg 188350, Russia
Varfolomeeva, E
[1
]
Sukhareva, E
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h-index: 0
机构:
Petersburg Nucl Phys Inst, St Petersburg 188350, RussiaPetersburg Nucl Phys Inst, St Petersburg 188350, Russia
Sukhareva, E
[1
]
Shabalina, E
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h-index: 0
机构:
Petersburg Nucl Phys Inst, St Petersburg 188350, RussiaPetersburg Nucl Phys Inst, St Petersburg 188350, Russia
Shabalina, E
[1
]
Drobchenko, E
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h-index: 0
机构:
Petersburg Nucl Phys Inst, St Petersburg 188350, RussiaPetersburg Nucl Phys Inst, St Petersburg 188350, Russia
Drobchenko, E
[1
]
Filatov, M
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机构:
Petersburg Nucl Phys Inst, St Petersburg 188350, RussiaPetersburg Nucl Phys Inst, St Petersburg 188350, Russia
Filatov, M
[1
]
机构:
[1] Petersburg Nucl Phys Inst, St Petersburg 188350, Russia
来源:
ATLA-ALTERNATIVES TO LABORATORY ANIMALS
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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.