Godden P M, Kass G, Mayer R T, Burke M D
Department of Biochemistry, University of Surrey, Guildford, U.K.
Biochem Pharmacol. 1987 Oct 15;36(20):3393-8. doi: 10.1016/0006-2952(87)90316-9.
The rates of metabolism of phenoxazone and a homologous series of its ethers (alkoxyresorufins) by liver and lung microsomes of rats exposed to cigarette smoke were compared with the metabolism in rats pretreated with 3-methylcholanthrene (3MC) or phenobarbitone (PB). The rate of resorufin production was dependent on the length of the ether side chain. Liver and lung microsomes from control rats differed in their activity profiles (rate of resorufin production plotted against side-chain length), showing highest activity with ethoxy- and benzyloxyresorufin respectively. 3MC and PB selectively induced hepatic microsomal resorufin production with only certain of the substrates and the two agents differed in their selectivity, inducing most greatly with ethoxy- and benzyloxyresorufin respectively. Pulmonary microsomal resorufin production was induced by 3MC with a substrate selectivity similar to that shown for liver, but PB suppressed pulmonary metabolism with all the substrates. A single, short exposure to cigarette smoke induced ethoxyresorufin O-deethylase activity transiently in liver and lung microsomes. Three consecutive daily short exposures to cigarette smoke caused a weak 3MC-like induction of liver microsomal alkoxyresorufin metabolism, but the effect on lung microsomes was like weak 3MC and PB inductions combined. It is concluded that cigarette smoke induces selected cytochrome P-450-linked alkoxyresorufin O-dealkylase activities to a similar extent in both lung and liver and that the effects of cigarette smoke are characteristic of both 3MC-type and non-3MC-type inducers.
将暴露于香烟烟雾的大鼠肝脏和肺微粒体对吩恶嗪及其一系列醚类同系物（烷氧基试卤灵）的代谢速率，与用3 - 甲基胆蒽（3MC）或苯巴比妥（PB）预处理的大鼠的代谢情况进行了比较。试卤灵的生成速率取决于醚侧链的长度。对照大鼠的肝脏和肺微粒体在其活性图谱（试卤灵生成速率相对于侧链长度作图）上有所不同，分别对乙氧基试卤灵和苄氧基试卤灵表现出最高活性。3MC和PB仅对某些底物选择性诱导肝微粒体试卤灵的生成，且这两种试剂的选择性不同，分别对乙氧基试卤灵和苄氧基试卤灵诱导作用最强。3MC以与肝脏相似的底物选择性诱导肺微粒体试卤灵的生成，但PB抑制了所有底物的肺代谢。单次短时间暴露于香烟烟雾可使肝脏和肺微粒体中的乙氧基试卤灵O - 脱乙基酶活性短暂升高。连续三天每天短时间暴露于香烟烟雾会导致肝脏微粒体烷氧基试卤灵代谢出现类似3MC的微弱诱导作用，但对肺微粒体的影响类似于3MC和PB诱导作用的联合效果。结论是，香烟烟雾在肺和肝脏中以相似程度诱导选定的细胞色素P - 450相关的烷氧基试卤灵O - 脱烷基酶活性，并且香烟烟雾的作用具有3MC型和非3MC型诱导剂的特征。
