A constitutive deficiency in the monooxygenase system of spontaneous mouse liver tumors.
A constitutive deficiency in the monooxygenase system of spontaneous mouse liver tumors.
复制标题
自发性小鼠肝脏肿瘤的单加氧酶系统的组成性缺陷。
DOI：
10.1093/carcin/5.6.785
复制
发表时间：
1984
期刊：
影响因子：
4.7
通讯作者：
D. Stout
中科院分区：
文献类型：
--
作者：
F. Becker;D. Stout
暴露于化学致癌物可引起肝细胞改变，表现出单加氧酶活性显著降低。有人认为，这种改变允许靶细胞逃避致癌物质的毒性作用并增殖。为了确定这种酶缺陷是否对致癌过程有更广泛的影响，我们研究了具有肿瘤发生遗传易感性的小鼠自发性肝细胞肿瘤的单加氧酶系统和其他成分。这些肿瘤均表现出细胞色素P-450和氨基比林N-脱甲基酶的显着缺陷，尽管没有已知的致癌物质，毒素，或促进剂在其环境中。由一个小的，单一的新生儿二乙基亚硝胺管理引起的类似组织型的肿瘤表现出相同的变化。因此，这份报告表明，在自发性肿瘤中，肿瘤发生的遗传程序和单加氧酶系统的缺陷之间存在着密切的联系。此外，它揭示了具有这种表型的细胞群的扩增不需要毒性选择性环境。
Exposure to chemical carcinogens evokes a population of altered hepatocytes that demonstrates significantly diminished monooxygenase activity. It has been suggested that this alteration permits the target cell to escape the toxic effects of the carcinogen and proliferate. In an attempt to determine whether this enzyme defect has broader implications for the carcinogenic process, we examined the monooxygenase system and additional components of spontaneous hepatocellular tumors in mice with a genetic predisposition to tumorigenesis. These tumors uniformly demonstrated a significant deficit in cytochrome P-450 and aminopyrine N-demethylase, despite the absence of known carcinogens, toxins, or promoting agents in their environment. Tumors of similar histiotype induced by a small, single neonatal administration of diethylnitrosamine demonstrated identical alterations. This report, therefore, suggests a strong link between a genetic program for tumorigenesis and a deficit in the monooxygenase system in spontaneous tumors. Further, it reveals that a toxic-selective environment is not required for the expansion of the cell population that possesses this phenotype.