Enhancement of misonidazole cytotoxicity by iron.

Enhancement of misonidazole cytotoxicity by iron.
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铁增强米索硝唑的细胞毒性。

DOI:
10.1080/09553008514552251
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发表时间:
1986
期刊:
International journal of radiation biology and related studies in physics, chemistry, and medicine
影响因子:
--
通讯作者:
Brown,JM
Brown,JM
中科院分区:
--
文献类型:
--
作者:
Samuni,A;Bump,EA;Mitchell,JB;Brown,JM

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Fe(III)-EDTA增强米索硝唑(misonidazole, MISO)对无血清培养液中低氧中国仓鼠卵巢(CHO)细胞的毒性。2µmFe(III)-EDTA可使MISO细胞毒性增强1.6倍,而200µmFe(III)-EDTA可使MISO增敏2.0倍。铁螯合剂desferal对CHO细胞具有抗MISO低氧细胞毒性的保护作用(100 μ desferal的保护因子约为2.5)。在中国仓鼠V79细胞中也得到了类似的结果。Fe(III)-EDTA还增强了[2-14C] MISO与细胞大分子的结合,而desferal则降低了MISO与细胞大分子的结合。这些结果表明,铁在MISO的还原性代谢中起重要作用,细胞内金属离子状态的修饰可能是调节硝基化合物生物学效应的有效途径。
The toxicity of misonidazole (MISO) to hypoxic Chinese hamster ovary (CHO) cells in serum-free medium is enhanced by Fe(III)-EDTA. Enhancement of MISO cytotoxicity by a factor of 1·6 was seen with 2µmFe(III)-EDTA, while 200 µmFe(III)-EDTA results in sensitization by a factor of 2·0. Treatment of CHO cells with the iron chelator desferal resulted in protection against the hypoxic cytotoxicity in MISO (approximate protection factor of 2·5 with 100 µmdesferal). Similar results were obtained with Chinese hamster V79 cells. Fe(III)-EDTA also enhanced binding of [2-14C] MISO to cellular macromolecules while desferal decreased binding of MISO to cellular macromolecules. These results suggest that iron plays an important role in the reductive metabolism of MISO and that modification of the intracellular metal ion status may be a useful approach to modulating the biological effect of nitro compounds.
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DOI: --
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