Olson J W, Weiner M
Res Commun Chem Pathol Pharmacol. 1980 Oct;30(1):71-89.
The hepatic cyclic nucleotide system and hepatic monooxygenase activity were examined in male rats following intramuscular or subcutaneous Walker 256 carcinosarcoma transplantation. Twelve days of continuous s.c. tumor growth significantly increased hepatic cyclic AMP levels, while levels of cyclic GMP, cytochrome P-450, cytochrome b-5, and p-chloro-N-methylaniline metabolism were significantly decreased. Whole blood from 6 day i.m. tumor-bearing rats incubated with liver slices obtained from non-tumor-bearing rats produced significantly elevated hepatic cyclic AMP levels concurrent with significantly depressed hepatic p-chloro-N-methylaniline metabolism. The chronological monitoring of tumor growth demonstrated a close temporal relationship between decreased cyclic AMP-dependent protein kinase activity, microsomal metabolism of p-chloro-N-methylaniline, and the mixed-function oxidase system. Significant changes in these hepatic enzyme systems occurred as early as 17 hours following tumor transplantation. At this same time, sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed the appearance of a 184,000 molecular weight protein in hepatic tissue from all tumor-bearing rats. These studies are compatible with the proposal that the hepatic cyclic AMP system may modulate toxohormone effects on hepatic drug biotransformation.
在雄性大鼠经肌肉或皮下接种Walker 256癌肉瘤后，对其肝脏环核苷酸系统和肝脏单加氧酶活性进行了检测。连续皮下肿瘤生长12天显著增加了肝脏环磷酸腺苷（cAMP）水平，而环磷酸鸟苷（cGMP）、细胞色素P - 450、细胞色素b - 5以及对氯 - N - 甲基苯胺代谢水平则显著降低。将接种肿瘤6天的大鼠的全血与取自未接种肿瘤大鼠的肝切片一起孵育，可使肝脏cAMP水平显著升高，同时肝脏对氯 - N - 甲基苯胺代谢显著降低。对肿瘤生长的时序监测表明，环磷酸腺苷依赖性蛋白激酶活性降低、对氯 - N - 甲基苯胺的微粒体代谢以及混合功能氧化酶系统之间存在密切的时间关系。这些肝脏酶系统的显著变化早在肿瘤移植后17小时就已出现。与此同时，十二烷基硫酸钠 - 聚丙烯酰胺凝胶电泳分析显示，所有接种肿瘤大鼠的肝脏组织中出现了一种分子量为184,000的蛋白质。这些研究结果与肝脏环磷酸腺苷系统可能调节毒素激素对肝脏药物生物转化作用的观点相符。
