BUTHIONINE SULFOXIMINE PROTECTS THE VIABILITY OF ADULT-RAT LEYDIG-CELLS EXPOSED TO ETHANE DIMETHANESULFONATE

被引:12
作者
KELCE, WR
机构
[1] ManTech Environmental Technology Inc., NC 27709, P.O. Box 12313. 2 Triangle Drive, Research Triangle Park
关键词
D O I
10.1006/taap.1994.1069
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Exposure to (EDS) in vivo or in vitro alters adult rat Leydig cell function within 3 hr and these cells subsequently die within 24-48 hr. Previously, we determined that reducing intracellular glutathione levels with buthionine sulfoximine (BSO) protects adult rat Leydig cell function during short-term (3 hr) EDS exposures. The present study extends these observations by assessing whether BSO also can prevent Leydig cell death following EDS exposure. To assess whether BSO can prevent EDS-induced Leydig cell death, Leydig cells were cultured in the presence or the absence of 4 mM BSO (12 hr), and subsequently with increasing doses of EDS (3 hr). The effects of EDS on Leydig cell death were estimated using a cytotoxicity assay (MTT assay) and by assessing the ability of adult rat Leydig cells to maintain LH-stimulated testosterone production and [S-35]- methionine incorporation 24 hr following EDS exposure. This culture duration was chosen because sustained alterations in MTT reduction, LH-stimulated testosterone production, and [S-35]methionine incorporation 24 hr following EDS exposure were found to reflect alterations in Leydig cell viability. The results suggest that lowering intracellular levels of glutathione with BSO prevents EDS-induced Leydig cell death. Restoring intracellular levels of glutathione with glutathione ethyl ester (8 mM) in the presence of BSO also restored the ability of EDS to kill Leydig cells. Taken together, these data suggest that glutathione mediates the mechanism by which EDS kills adult rat Leydig cells. (C) 1994 Academic Press, Inc.
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页码:237 / 246
页数:10
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