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采用一氧化碳差光谱法检测乙双吗啉(AT—1727)和丙双吗啉(AT—2153)等抗肿瘤药物对大鼠肝微粒体细胞色素P_(450)含量的影响。实验发现苯巴比妥对肝微粒体细胞色素P_(450)的诱导作用是对照组的3.6倍,而CCl_4抑制P_(450)的产生,为对照组的40％。AT—1727和AT—2153在50mg/kg大剂量时,对大鼠肝微粒体细胞色素P_(450)含量有轻度诱导作用,但不明显。AT—1727和AT—2153在1.25和25mg/kg时,使大鼠肝微粒体P_(450)含量降低,约为对照组的80—86％。AT—1727在25mg/kg时能抑制苯巴比妥诱导肝微粒体P_(450),AT—2153在25mg/kg时对苯巴比妥诱导肝微粒体P_(450)的作用则无影响。
Carbon monoxide difference spectroscopy was used to detect the effect of antitumor drugs such as ethanedimorpholine (AT-1727) and propanedimorpholine (AT-2153) on cytochrome P450 content in rat liver microsomes. It was found that phenobarbital had 3.6-fold induction of hepatic microsomal cytochrome P 450 in the control group, while CCl 4 inhibited the production of P 450 in 40% of the control group. When AT-1727 and AT-2153 were given at a high dose of 50 mg/kg, they slightly induced the cytochrome P 450 content of liver microsomes, but it was not obvious. When AT-1727 and AT-2153 were used at 1.25 and 25 mg/kg, the P_(450) content of liver microsomes decreased, which was about 80–86% of the control group. AT-1727 inhibited phenobarbital-induced hepatic microsomal P450 at 25 mg/kg, while AT-2727 had no effect on phenobarbital-induced hepatic microsomal P450 at 25 mg/kg.