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Depletion of a discrete nuclear glutathione pool by oxidative stress, but not by buthionine sulfoximine. Correlation with enhanced alkylating agent cytotoxicity to human melanoma cells in vitro.

Abstract：

:The existence of a distinct pool of glutathione in the nucleus of cultured human melanoma cells was demonstrated. Melanoma cell nuclei contained 13-35 pmol of glutathione/10(6) nuclei, or approximately 0.4-1.3% of the total cellular glutathione. This nuclear glutathione pool resisted depletion by buthionine sulfoximine, an agent that inhibits glutathione synthesis, but was rapidly and reversibly depleted by subtoxic concentrations of Adriamycin plus carmustine, two agents that promote oxidation of glutathione without permitting its regeneration through enzymatic reduction of glutathione disulfide. The ability of Adriamycin plus carmustine to deplete this small but significant pool of glutathione in the cell nucleus may explain why these agents potentiate the cytotoxic effects of the DNA-alkylating agent melphalan to a much higher degree than does buthionine sulfoximine at concentrations that are equipotent in depleting cytosolic glutathione.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Jevtović-Todorović V,Guenthner TM

doi

10.1016/0006-2952(92)90540-y

subject

Has Abstract

pub_date

1992-10-06 00:00:00

pages

1383-93

issue

7

eissn

0006-2952

issn

1873-2968

pii

0006-2952(92)90540-Y

journal_volume

44

pub_type

杂志文章

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