Focal nuclear hepatocyte response to oxidative damage following low dose thioacetamide intoxication
Focal nuclear hepatocyte response to oxidative damage following low dose thioacetamide intoxication
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DOI：
10.1093/carcin/18.8.1663
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发表时间：
1997-08-01
期刊：
影响因子：
4.7
通讯作者：
Weisz, J
中科院分区：
文献类型：
--
作者：
Clawson, GA;Benedict, CM;Weisz, J
用低剂量的肝癌物质硫代乙酰胺治疗大鼠。治疗后四十八小时，观察到肝损伤的微观病灶，其周围环绕着组织学正常肝细胞的外周边缘。这些外周肝细胞通常含有增大的细胞核，并显示 4-羟基壬烯醛-蛋白加合物的核染色，表明核氧化损伤。在这些相同的肝细胞中，我们还观察到 mu 类谷胱甘肽-S-转移酶和乙醇脱氢酶 I 的特异性局灶核诱导，这两种酶对 4-羟基壬烯醛的代谢很重要。特别令人感兴趣的是 APE/ref-1（一种可以充当氧化还原因子的多功能 DNA 修复酶）和转录因子 Jun 的同时核诱导，APE/ref-1 促进其 DNA 结合。这些结果记录了对硫代乙酰胺给药产生的氧化损伤的精心安排的局灶性核反应，并且可能与这种治疗产生的永久性影响有关。
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.