English J C, Anders M W
Drug Metab Dispos. 1985 Jul-Aug;13(4):449-52.
Carbon tetrachloride administration to rats produced a selective loss of hepatic cytochrome P-450-dependent catalytic activities. Of the cytochrome P-450-dependent catalytic activities tested, the metabolism of carbon tetrachloride to phosgene and the low Km N-nitrosodimethylamine demethylase were the most sensitive to destruction by carbon tetrachloride. A 50% or greater loss in these catalytic activities was observed 3 hr after giving 10 microliters carbon tetrachloride/kg. Related catalytic activities, such as the microsomal metabolism of carbon tetrachloride to chloroform and the high Km N-nitrosodimethylamine demethylase, were diminished less than 20% 3 hr after giving 10 microliters carbon tetrachloride/kg. To investigate further the relationship between the metabolism of N-nitrosodimethylamine and carbon tetrachloride, the effect of pyrazole, a known inducer of the low Km N-nitrosodimethylamine demethylase, on carbon tetrachloride metabolism was studied. Pyrazole treatment produced a 5.6-fold increase in the microsomal metabolism of carbon tetrachloride to phosgene and a 1.9-fold increase in the conversion of carbon tetrachloride to chloroform. The similarities between both the loss and the induction of the low Km N-nitrosodimethylamine demethylase and the metabolism of carbon tetrachloride to phosgene suggest that these catalytic activities represent a common isozyme of cytochrome P-450. Analysis of cytochromes P-450 by HPLC provided evidence for an isozyme of cytochrome P-450 inducible by pyrazole and destroyed by carbon tetrachloride.
给大鼠注射四氯化碳会导致肝脏中细胞色素P - 450依赖的催化活性选择性丧失。在所测试的细胞色素P - 450依赖的催化活性中，四氯化碳代谢为光气以及低Km值的N - 亚硝基二甲胺脱甲基酶对四氯化碳的破坏最为敏感。给予10微升四氯化碳/千克后3小时，这些催化活性丧失了50%或更多。相关的催化活性，如微粒体将四氯化碳代谢为氯仿以及高Km值的N - 亚硝基二甲胺脱甲基酶，在给予10微升四氯化碳/千克后3小时减少不到20%。为了进一步研究N - 亚硝基二甲胺代谢与四氯化碳之间的关系，研究了吡唑（一种已知的低Km值N - 亚硝基二甲胺脱甲基酶诱导剂）对四氯化碳代谢的影响。吡唑处理使微粒体将四氯化碳代谢为光气的能力增加了5.6倍，将四氯化碳转化为氯仿的能力增加了1.9倍。低Km值N - 亚硝基二甲胺脱甲基酶的丧失和诱导以及四氯化碳代谢为光气之间的相似性表明，这些催化活性代表了细胞色素P - 450的一种共同同工酶。通过高效液相色谱法对细胞色素P - 450进行分析，为一种可被吡唑诱导且被四氯化碳破坏的细胞色素P - 450同工酶提供了证据。
