Belisario M A, Pecce R, Battista C, Panza N, Pacilio G
Biomed Pharmacother. 1985;39(8):445-8.
Cyclophosphamide (CP) metabolites, rather than the parent compound, show mutagenic activity towards Salmonella typhimurium TA 1535 tester strain when S9 fraction from phenobarbital (PB)-induced rat liver is used as in vitro metabolizing system. On the other hand, inhibition of CP in vitro mutagenicity was observed by adding increasing amounts of beta-carotene (beta-C) to the system. A typical dose-dependent mutagenic response was observed by assaying 24 h urine samples of PB-induced rats injected i.p. with different amounts of CP. Addition of beta-C to urines of CP-treated rats failed to inhibit their mutagenicity. Conversely, a marked decrease in urine mutagenicity was observed when rats were simultaneously treated with the two drugs. These data show that beta-carotene partially inhibits, in vitro and in vivo, CP metabolism via hepatic mixed-function oxidase enzymes to mutagenic species.
当使用来自苯巴比妥（PB）诱导的大鼠肝脏的S9组分作为体外代谢系统时，环磷酰胺（CP）的代谢产物而非母体化合物对鼠伤寒沙门氏菌TA 1535测试菌株显示出诱变活性。另一方面，通过向系统中添加越来越多的β-胡萝卜素（β-C），观察到CP体外诱变性受到抑制。通过检测经腹腔注射不同剂量CP的PB诱导大鼠的24小时尿液样本，观察到典型的剂量依赖性诱变反应。向CP处理大鼠的尿液中添加β-C未能抑制其诱变性。相反，当大鼠同时用这两种药物处理时，观察到尿液诱变性显著降低。这些数据表明，β-胡萝卜素在体外和体内通过肝脏混合功能氧化酶将CP代谢为诱变物质的过程中起到部分抑制作用。
