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

被引:8
作者
Clawson, GA
Benedict, CM
Kelley, MR
Weisz, J
机构
[1] PENN STATE UNIV, MILTON S HERSHEY MED CTR, SCH MED, DEPT BIOCHEM & MOL BIOL, HERSHEY, PA 17033 USA
[2] PENN STATE UNIV, MILTON S HERSHEY MED CTR, SCH MED, DEPT OBSTET & GYNECOL, HERSHEY, PA 17033 USA
[3] INDIANA UNIV, SCH MED, DEPT BIOCHEM & MOL BIOL, INDIANAPOLIS, IN USA
关键词
D O I
10.1093/carcin/18.8.1663
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 mu-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.
引用
收藏
页码:1663 / 1668
页数:6
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