Hill D L, Kirk M C, Struck R F
Cancer Res. 1975 Feb;35(2):296-301.
N, N-Bis (2-chloroethyl)-N-nitrosourea (BCNU) is a substrate for a microsomal enzyme of mouse liver. The reaction requires NADPH, and the product is 1, 3-bis (2-chloroethyl) urea. This activity is also found in mouse lungs but not in several other tissues. With reaction conditions under which BCNU is not chemically degraded, the Km for BCNU with liver microsomes is 1.7 mM; nicotine is a competitive inhibitor with a Ki of 0.6 mM. N-Methyl-N-nitrosourea is denitrosated in a similar reaction. N- (2-Chloroetyhy)- N-cyclohexyl-N-nitrosourea and N-(2-chloroethyl)-N-(trans-4-methylcyclohexyl)-N-nitrosourea are also substrates for microsomal enzymes, but the products of these reactions are ring-hydroxylated derivatives. The Km value for N-(2-CHLOROETHYL)-N-cyclohexyl-N-nitrosourea is 3.0 mM and that for N-(2-chloroethyl)-N-(trans-4-methylcyclohexyl)-N-nitrosourea is 1.0 mM. The hydroxylase activity is also present in lungs, but not in the other mouse tissues. The rates of microsomal metabolism of BCNU, N-(2-chloroethyl)-N-cyclohexyl-N-nitrosourea, and N-(2-chloroethyl)-N-cyclohexyl-N-nitrosourea, and N-(2-chloroethyl-N-(trans-4-methylcyclohexyl)-N-nitrosourea are fast enough to allow metabolism of large portions of administered doses before chemical decomposition of the drugs occurs.
N，N-双（2-氯乙基）-N-亚硝基脲（卡莫司汀，BCNU）是小鼠肝脏微粒体酶的一种底物。该反应需要还原型辅酶Ⅱ（NADPH），产物是1，3-双（2-氯乙基）脲。这种活性在小鼠肺中也能发现，但在其他几种组织中未发现。在BCNU没有化学降解的反应条件下，肝脏微粒体对BCNU的米氏常数（Km）为1.7毫摩尔；尼古丁是一种竞争性抑制剂，其抑制常数（Ki）为0.6毫摩尔。N-甲基-N-亚硝基脲在类似反应中发生脱亚硝基作用。N-（2-氯乙基）-N-环己基-N-亚硝基脲和N-（2-氯乙基）-N-（反式-4-甲基环己基）-N-亚硝基脲也是微粒体酶的底物，但这些反应的产物是环羟基化衍生物。N-（2-氯乙基）-N-环己基-N-亚硝基脲的Km值为3.0毫摩尔，N-（2-氯乙基）-N-（反式-4-甲基环己基）-N-亚硝基脲的Km值为1.0毫摩尔。羟化酶活性在肺中也存在，但在其他小鼠组织中不存在。BCNU、N-（2-氯乙基）-N-环己基-N-亚硝基脲以及N-（2-氯乙基）-N-（反式-4-甲基环己基）-N-亚硝基脲的微粒体代谢速率足够快，能够在药物发生化学分解之前代谢大部分给药剂量。
