TY - JOUR
T1 - Focal nuclear hepatocyte response to oxidative damage following low dose thioacetamide intoxication
AU - Clawson, Gary A.
AU - Benedict, Catharine M.
AU - Kelley, Mark R.
AU - Weisz, Judith
PY - 1997/8
Y1 - 1997/8
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.
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U2 - 10.1093/carcin/18.8.1663
DO - 10.1093/carcin/18.8.1663
M3 - Article
C2 - 9276646
AN - SCOPUS:0031431890
SN - 0143-3334
VL - 18
SP - 1663
EP - 1668
JO - Carcinogenesis
JF - Carcinogenesis
IS - 8
ER -