Distinctive biochemical pattern associated with resistance of hepatocytes in hepatocyte nodules during liver carcinogenesis.
Distinctive biochemical pattern associated with resistance of hepatocytes in hepatocyte nodules during liver carcinogenesis.
复制标题
肝癌发生过程中与肝细胞结节中肝细胞抗性相关的独特生化模式。
DOI：
10.1289/ehp.8349171
复制
发表时间：
1983-03
影响因子：
10.4
通讯作者：
中科院分区：
文献类型：
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作者：
由二乙基亚硝胺引发并通过饮食2-乙酰氨基芴加部分肝切除术（“抗性肝细胞模型”）选择的肝细胞（“增生性”）结节具有特殊的生化行为和代谢活性模式，与许多外源性物质（包括许多促进剂和致癌物）急性观察到的不同。相对于周围和正常肝脏，结节细胞对2-乙酰氨基芴的摄取非常低，细胞色素P-450和芳烃羟化酶的活性水平低，γ-谷氨酰转移酶、微粒体环氧化物水解酶、可溶性谷胱甘肽-S-转移酶和可溶性UDP-葡糖醛酸转移酶（UDP-GT 1）的活性水平高，谷胱甘肽水平升高。这种代谢模式似乎使结节对外源性物质（如2-乙酰氨基芴）的抗性最大化，从而可能解释结节肝细胞对2-乙酰氨基芴和其他致癌物抑制细胞增殖和细胞毒性的抗性行为。这似乎是新的代谢程序在致癌作用的可能重要性进行了简要讨论。
Hepatocyte (“hyperplastic”) nodules induced in the liver by initiation with diethylnitrosamine and selected by dietary 2-acetylaminofluorene plus partial hepatectomy (“resistant hepatocyte model”) have a special pattern of biochemical behavior and metabolic activity different than that seen acutely with many xenobiotics including many promoting agents and carcinogens. The nodule cells show a very low uptake of 2-acetylaminofluorene, relative to surrounding and normal liver, low levels of activity in the cytochromes P-450 and aryl hydrocarbon hydroxylase, high levels of activity in γ-glutamyltransferase, microsomal epoxide hydrolase, soluble glutathione-S-transferase and soluble UDP-glucuronyltransferase (UDP-GT1) and elevated levels of glutathione. This metabolic pattern appears to maximize the resistance of the nodules to xenobiotics generally, such as 2-acetylaminofluorene, and thereby may account for the resistant behavior of nodule hepatocytes to the inhibition of cell proliferation and the cytotoxicity by 2-acetylaminofluorene and other carcinogens. The possible importance of this seemingly new metabolic program in carcinogenesis is discussed briefly.