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

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

Research output: Contribution to journalArticle

8 Citations (Scopus)

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

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Thioacetamide
Hepatocytes
Multifunctional Enzymes
DNA Repair Enzymes
Alcohol Dehydrogenase
Glutathione Transferase
Oxidation-Reduction
Transcription Factors
Staining and Labeling
Liver
DNA
Wounds and Injuries
Enzymes
Proteins
4-hydroxy-2-nonenal

ASJC Scopus subject areas

  • Cancer Research

Cite this

Focal nuclear hepatocyte response to oxidative damage following low dose thioacetamide intoxication. / Clawson, Gary A.; Benedict, Catharine M.; Kelley, Mark; Weisz, Judith.

In: Carcinogenesis, Vol. 18, No. 8, 08.1997, p. 1663-1668.

Research output: Contribution to journalArticle

Clawson, Gary A. ; Benedict, Catharine M. ; Kelley, Mark ; Weisz, Judith. / Focal nuclear hepatocyte response to oxidative damage following low dose thioacetamide intoxication. In: Carcinogenesis. 1997 ; Vol. 18, No. 8. pp. 1663-1668.
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