1, 2-dithiol-3-thione analogs: Effects on NAD(P)H: Quinone reductase and glutathione levels in murine hepatoma cells

Mary J.de Long, Patrick Dolan, Annette B. Santamaria, Ernest Bueding

Research output: Contribution to journalArticle

Abstract

The 1, 2-dithiol-3-thiones are a class of five-membered cyclic sulfur compounds which have chemotherapeutic and chemoprotective properties. The parent 1, 2-dithiol-3-thione nucleus and a series of six substituted analogs all induced NAD(P)H: quinone reductase (EC 1.6.99.2) activity and elevated glutathione levels in Hepa 1c1c7 murine hepatoma cells in culture thereby enhancing detoxification potential. These analogs included monosubstituted derivatives with phenyl, p-methoxy-phenyl or 2-pyrazinyl groups at C-4 or C-5, and disubstituted compounds bearing phenyl or 2-pyrazinyl moieties at C-5 and an additional methyl group at C-4. This system can be used as an in vitro model for the study of the specificity and mechanism of action of the 1, 2-dithiol-3-thiones as already demonstrated for several other classes of chemoprotective agents. The 1, 2-dithiol-3-thiones also elevated quinone reductase and glutathione levels in the Hepa 1c1c7 cell mutants (BPrc1 and TAOBPrc1) that are defective in aryl hydrocarbon receptor functions. We conclude that the 1, 2-dithiol-3-thiones are largely concerned with the stimulation of metabolic inactivation of electrophiles.

Original languageEnglish (US)
Pages (from-to)977-980
Number of pages4
JournalCarcinogenesis
Volume7
Issue number6
DOIs
StatePublished - Jun 1 1986

ASJC Scopus subject areas

  • Cancer Research

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