Tong S, Hirokata Y, Litterst C L, Gram T E
Chem Biol Interact. 1984 Apr;49(1-2):105-19. doi: 10.1016/0009-2797(84)90055-3.
Effects of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) on the hepatic mixed-function oxidase system in male rats were studied both in vivo and in vitro. A single dose of CCNU (40 mg/kg) caused a significant reduction in hepatic mixed-function oxidase activities within 3 days after administration. The depression was prolonged for cytochrome P-450, total haem and the metabolism of several type I substrates lasting up to 10 weeks after a single dose. By contrast, aniline hydroxylase, cytochrome b5 and NADPH-cytochrome c reductase activities returned to near control levels after week two. Microsomal enzymes in the kidneys of treated animals however, were unaltered. Serum glutamic pyruvic and glutamic oxaloacetic transaminase and bilirubin levels, indicators of hepatotoxicity, were greatly elevated 3 days after CCNU treatment. These parameters fell rapidly but were still above control levels to the end of the 10-week study. When added in vitro, CCNU reduced apparent cytochrome P-450 content and the metabolism of type I substrates in microsomes from untreated, phenobarbital (PB) and 3-methylcholanthrene (3-MC)-pretreated rats. Total haem and NADPH-cytochrome c reductase were not affected whereas aniline hydroxylase activity was activated. CCNU interacted with hepatic microsomes to produce a type I difference spectrum.
研究了1-(2-氯乙基)-3-环己基-1-亚硝基脲（CCNU）对雄性大鼠肝脏混合功能氧化酶系统的体内和体外作用。单次给予CCNU（40mg/kg）后3天内，肝脏混合功能氧化酶活性显著降低。细胞色素P-450、总血红素以及几种I型底物的代谢受到的抑制持续延长，单次给药后长达10周。相比之下，苯胺羟化酶、细胞色素b5和NADPH-细胞色素c还原酶活性在第二周后恢复到接近对照水平。然而，处理动物肾脏中的微粒体酶未发生改变。CCNU处理3天后，血清谷丙转氨酶、谷草转氨酶和胆红素水平（肝毒性指标）大幅升高。这些参数迅速下降，但在10周研究结束时仍高于对照水平。体外添加时，CCNU降低了未处理、苯巴比妥（PB）和3-甲基胆蒽（3-MC）预处理大鼠微粒体中细胞色素P-450的表观含量和I型底物的代谢。总血红素和NADPH-细胞色素c还原酶未受影响，而苯胺羟化酶活性被激活。CCNU与肝脏微粒体相互作用产生I型差异光谱。
