Focal nuclear hepatocyte response to oxidative damage following low dose thioacetamide intoxication

Gary A. Clawson, Catharine M. Benedict, Mark R. Kelley, Judith Weisz

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Rats were treated with low doses of the hepatocarcinogen thioacetamide. Forty-eight hours following this treatment, microscopic foci of hepatic injury were observed, which were surrounded by a peripheral rim of histologically normal hepatocytes. These peripheral hepatocytes generally contained enlarged nuclei, and showed nuclear staining for 4-hydroxynonenal-protein adducts, indicative of nuclear oxidative damage. In these same hepatocytes, we also observed specific focal nuclear induction of μ-class glutathione-S-transferase and alcohol dehydrogenase I, two enzymes which are important in metabolism of 4-hydroxynonenal. Of particular interest was the concurrent nuclear induction of APE/ref-1, a multifunctional DNA repair enzyme which can function as a redox factor, and of the transcription factor Jun, whose DNA binding is facilitated by APE/ref-1. These results document an orchestrated focal nuclear response to oxidative damage produced by thioacetamide administration, and may relate to the permanent effects produced by this treatment.

Original languageEnglish (US)
Pages (from-to)1663-1668
Number of pages6
JournalCarcinogenesis
Volume18
Issue number8
DOIs
StatePublished - Aug 1 1997

ASJC Scopus subject areas

  • Cancer Research

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