Zimmer D M, Bhuyan B K
Mutat Res. 1976 Nov;40(4):281-8. doi: 10.1016/0165-1218(76)90026-4.
The following nitrosourea compounds were compared for their ability to induce mutation (to histidine independence) in the histidine-requiring auxotroph Salmonella typhimurium his G46: MNU, streptozotocin (SZ, streptozocin) and its analogs SZA1 and SZA2, and the antitumor drugs BCNU, CCNU and DCNU. At equitoxic doses SZ, SZA1, SZA2 and MNU were almost equally mutagenic causing 150, 42, 140 and 170 mutants/106 survivors at 20% lethal dose (ID20) ALTHOUGH, ON A WIEGHT BASIS, SZ was the most mutagenic of all the compounds tested. At ID20 BCNU, CCNU and DCNU gave about 0.5 mutants/106 survivors. Our results show that these nitrosoureas, in common with many other drugs (such as cyclophosphamide, daunomycin, etc.) used in cancer chemotherapy, are highly mutagenic. The implication of our results in the screening of drugs for their mutagenicity to man is discussed.
对以下亚硝基脲化合物在需组氨酸的鼠伤寒沙门氏菌组氨酸营养缺陷型his G46中诱导突变(使其不依赖组氨酸)的能力进行了比较:N-甲基-N'-亚硝基脲(MNU)、链脲佐菌素(SZ,链佐星)及其类似物SZA1和SZA2,以及抗肿瘤药物卡莫司汀(BCNU)、洛莫司汀(CCNU)和司莫司汀(DCNU)。在同等毒性剂量下,SZ、SZA1、SZA2和MNU的致突变性几乎相同,在20%致死剂量(ID20)时分别导致150、42、140和170个突变体/106个存活菌,尽管按重量计算,SZ是所有测试化合物中致突变性最强的。在ID20时,BCNU、CCNU和DCNU产生约0.5个突变体/106个存活菌。我们的结果表明,这些亚硝基脲与癌症化疗中使用的许多其他药物(如环磷酰胺、柔红霉素等)一样,具有高度致突变性。讨论了我们的结果在筛选对人类有致突变性的药物方面的意义。