Roomi M W, Columbano A, Ledda-Columbano G M, Sarma D S
Carcinogenesis. 1986 Oct;7(10):1643-6. doi: 10.1093/carcin/7.10.1643.
Hepatocyte nodules in the rat exhibit a unique biochemical pattern which is characterized by a decrease in Phase I and an increase in Phase II components of the drug-metabolizing system. The present study was designed to determine whether this biochemical pattern is unique for rat hepatocyte nodules or is a property of the liver cell, but expressed only when the liver cell is perturbed. The results obtained indicate that lead nitrate (5 or 10 mumol/100 g body wt), an inducer of liver cell proliferation, caused a decrease in Phase I components such as microsomal cytochromes P-450 and in the activity of aminopyrine N-demethylase, while it caused an increase in Phase II components such as glutathione, and in the activities of glutathione-S-transferase and DT-diaphorase in rat liver. Of particular interest was the finding in liver cytosol of lead-treated rats of an increased content of a polypeptide which cross-reacts with the anti-rat placental form of glutathione-S-transferase. Recently, it has been shown that rat hepatocyte nodules exhibited an increased content of the placental form of glutathione-S-transferase. Thus, the results suggest that some chemicals, such as lead nitrate, can induce in rat liver a biochemical pattern similar in certain respects to that exhibited by hepatic nodules. These chemicals may be used as model compounds to understand the molecular mechanism(s) underlying the induction of new and unique biochemical machinery seen in hepatic nodules.
大鼠肝细胞结节呈现出一种独特的生化模式，其特征是药物代谢系统的I相成分减少，II相成分增加。本研究旨在确定这种生化模式是大鼠肝细胞结节所特有的，还是肝细胞的一种特性，只是在肝细胞受到干扰时才表现出来。所获得的结果表明，硝酸铅（5或10 μmol/100 g体重），一种肝细胞增殖诱导剂，导致I相成分如微粒体细胞色素P-450减少以及氨基比林N-脱甲基酶活性降低，同时导致II相成分如谷胱甘肽增加以及大鼠肝脏中谷胱甘肽-S-转移酶和DT-黄递酶活性增加。特别有趣的是，在铅处理大鼠的肝细胞溶胶中发现一种与抗大鼠胎盘形式的谷胱甘肽-S-转移酶发生交叉反应的多肽含量增加。最近，已经表明大鼠肝细胞结节呈现出胎盘形式的谷胱甘肽-S-转移酶含量增加。因此，结果表明一些化学物质，如硝酸铅，可在大鼠肝脏中诱导出在某些方面与肝结节所呈现的生化模式相似的生化模式。这些化学物质可用作模型化合物，以了解肝结节中所见新的和独特生化机制诱导背后的分子机制。
