铁增强米索硝唑的细胞毒性。

Enhancement of misonidazole cytotoxicity by iron.

作者信息

Samuni A, Bump E A, Mitchell J B, Brown J M

出版信息

Int J Radiat Biol Relat Stud Phys Chem Med. 1986 Jan;49(1):77-83. doi: 10.1080/09553008514552251.

Abstract

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 2 microM Fe(III)-EDTA, while 200 microM Fe(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 microM desferal). 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.

摘要

在无血清培养基中，乙二胺四乙酸铁（III）（Fe(III)-EDTA）可增强米索硝唑（MISO）对缺氧中国仓鼠卵巢（CHO）细胞的毒性。2微摩尔Fe(III)-EDTA可使MISO的细胞毒性增强1.6倍，而200微摩尔Fe(III)-EDTA可使致敏作用增强2.0倍。用铁螯合剂去铁胺处理CHO细胞可使其免受MISO的缺氧细胞毒性（100微摩尔去铁胺时的保护系数约为2.5）。中国仓鼠V79细胞也得到了类似结果。Fe(III)-EDTA还增强了[2-14C]MISO与细胞大分子的结合，而去铁胺则降低了MISO与细胞大分子的结合。这些结果表明，铁在MISO的还原代谢中起重要作用，改变细胞内金属离子状态可能是调节硝基化合物生物学效应的一种有用方法。