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

Gary Clawson, Catharine M. Benedict, Mark R. 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 (US)
Pages (from-to)1663-1668
Number of pages6
JournalCarcinogenesis
Volume18
Issue number8
DOIs
StatePublished - Aug 1 1997

Fingerprint

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

All Science Journal Classification (ASJC) codes

  • Cancer Research

Cite this

@article{8f843bad06954ab090ffa8c297e82548,
title = "Focal nuclear hepatocyte response to oxidative damage following low dose thioacetamide intoxication",
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.",
author = "Gary Clawson and Benedict, {Catharine M.} and Kelley, {Mark R.} and Judith Weisz",
year = "1997",
month = "8",
day = "1",
doi = "10.1093/carcin/18.8.1663",
language = "English (US)",
volume = "18",
pages = "1663--1668",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "8",

}

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

In: Carcinogenesis, Vol. 18, No. 8, 01.08.1997, p. 1663-1668.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Focal nuclear hepatocyte response to oxidative damage following low dose thioacetamide intoxication

AU - Clawson, Gary

AU - Benedict, Catharine M.

AU - Kelley, Mark R.

AU - Weisz, Judith

PY - 1997/8/1

Y1 - 1997/8/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0031431890&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031431890&partnerID=8YFLogxK

U2 - 10.1093/carcin/18.8.1663

DO - 10.1093/carcin/18.8.1663

M3 - Article

C2 - 9276646

AN - SCOPUS:0031431890

VL - 18

SP - 1663

EP - 1668

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 8

ER -