丁硫氨酸亚砜胺和SR2508在啮齿动物及人类细胞中的谷胱甘肽耗竭与细胞毒性

Glutathione depletion and cytotoxicity of buthionine sulphoximine and SR2508 in rodent and human cells.

作者信息

Ling C C, Wong R S, Basas R D

机构信息

Department of Radiation Oncology, University of California, San Francisco 94143.

出版信息

Int J Radiat Oncol Biol Phys. 1990 Feb;18(2):325-30. doi: 10.1016/0360-3016(90)90097-4.

DOI:10.1016/0360-3016(90)90097-4

PMID:2137437

Abstract

SR2508 (1 mM) increases the rate of glutathione (GSH) depletion by L-buthionine-S-R-sulphoximine (BSO) in hypoxic V79 rodent and A549 human cells. Specifically, the GSH content for V79 and A549 cells, after incubating for about 6 hr with 50 and 100 microM BSO, respectively, was lower by at least 10-fold when 1 mM SR2508 was present. In addition, 1 mM SR2508 is extremely toxic to hypoxic cells with lower GSH content. Survival probabilities of GSH-depleted V79 and A549 cells are about 10(-3) after 10 hr incubation with 1 mM SR2508. By itself, 1 mM SR2508 or 50-100 microM BSO decreased cellular viability by about 50% with a 10 hr treatment period. Both the phenomena described above are preferential towards hypoxic cells with minimal effect on aerobic cells.

摘要

SR2508（1毫摩尔）可提高低氧条件下的V79啮齿动物细胞和A549人细胞中，L-丁硫氨酸-S-亚砜亚胺（BSO）导致的谷胱甘肽（GSH）消耗速率。具体而言，在分别用50和100微摩尔BSO孵育约6小时后，当存在1毫摩尔SR2508时，V79和A549细胞中的GSH含量至少降低了10倍。此外，1毫摩尔SR2508对GSH含量较低的低氧细胞具有极高的毒性。在用1毫摩尔SR2508孵育10小时后，GSH耗尽的V79和A549细胞的存活概率约为10⁻³。单独使用时，1毫摩尔SR2508或50 - 100微摩尔BSO在10小时的处理期内可使细胞活力降低约50%。上述两种现象对低氧细胞具有选择性，对需氧细胞影响极小。