Franza B R, Oeschger N S, Oeschger M P, Schein P S
J Natl Cancer Inst. 1980 Jul;65(1):149-54.
The relative mutagenic activities of chloroethyl-nitrosourea and methylnitrosourea antitumor agents in active clinical use were determined with the use of the Ames Salmonella typhimurium assay. The results indicated that the drugs induced base substitutions. 2-Deoxy-2-[[(methylnitrosoamino)carbonyl]amino]-D-glucopyranose (also called streptozotocin), a glucose-containing methylnitrosourea, was the most mutagenic of all compounds tested and showed at least a 250-fold increase in activity when compared to that of its chloroethyl analog, 2-[[[(2-chloroethyl) nitrosoamino]carbonyl]-amino]-2-deoxy-D-glucose (also called chlorozotocin). All nitrosoureas, with the exception of N'-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-N-(2-chloroethyl)-N-nitrosourea monohydrochloride, a pyrimidine chloroethyl analog, demonstrated an increase in mutagenicity after incubation with induced Sprague-Dawley rat liver microsomes. No correlation between in vitro chemical alkylating activity and mutagenic potential was observed. Mutagenic activity was not observed to be of predictive value for antitumor activity in the L1210 leukemia model system.
利用鼠伤寒沙门氏菌Ames试验测定了目前临床使用的氯乙基亚硝基脲和甲基亚硝基脲类抗肿瘤药物的相对诱变活性。结果表明，这些药物诱导碱基置换。2-脱氧-2-[[(甲基亚硝基氨基)羰基]氨基]-D-吡喃葡萄糖（也称为链脲佐菌素），一种含葡萄糖的甲基亚硝基脲，是所有测试化合物中诱变活性最强的，与其氯乙基类似物2-[[[(2-氯乙基)亚硝基氨基]羰基]氨基]-2-脱氧-D-葡萄糖（也称为氯脲佐菌素）相比，其活性至少增加了250倍。除嘧啶氯乙基类似物N'-[(4-氨基-2-甲基-5-嘧啶基)甲基]-N-(2-氯乙基)-N-亚硝基脲盐酸盐外，所有亚硝基脲与诱导的斯普拉格-道利大鼠肝微粒体孵育后诱变活性均增加。未观察到体外化学烷基化活性与诱变潜力之间的相关性。在L1210白血病模型系统中，未观察到诱变活性对抗肿瘤活性具有预测价值。
