Andrews A W, Lijinsky W, Snyder S W
Mutat Res. 1984 Feb;135(2):105-8. doi: 10.1016/0165-1218(84)90162-9.
8 drugs that are amines or amides and that interact with nitrous acid to form potentially carcinogenic and mutagenic N-nitroso derivatives were tested for mutagenicity to Salmonella typhimurium. None of the compounds was mutagenic alone, with or without liver S9 activation. After reaction with nitrite in acetic acid solution, the products of 4 of the compounds were mutagenic. Diphenhydramine and hydrochlorothiazide gave products mutagenic with or without activation, but only to strain TA98. Methaphenilene gave products mutagenic to TA1538, TA98 and TA100 without microsomal activation. Dimethyldodecylamine-N-oxide after nitrosation was mutagenic with S9 activation to TA1535 indicating a response to the nitrosomethyldodecylamine formed. Allantoin, pyrilamine, chlorothen, methafurylene and thenyldiamine were not mutagenic alone or after nitrosation.
对8种为胺类或酰胺类且能与亚硝酸相互作用形成潜在致癌和致突变性N-亚硝基衍生物的药物进行了鼠伤寒沙门氏菌致突变性测试。这些化合物单独存在时,无论有无肝脏S9激活,均无致突变性。在乙酸溶液中与亚硝酸盐反应后,其中4种化合物的产物具有致突变性。苯海拉明和氢氯噻嗪的产物无论有无激活均具有致突变性,但仅对TA98菌株有作用。美沙芬林的产物在无微粒体激活的情况下对TA1538、TA98和TA100具有致突变性。亚硝化后的二甲基十二烷基胺-N-氧化物在S9激活下对TA1535具有致突变性,表明对形成的亚硝基甲基十二烷基胺有反应。尿囊素、吡苄明、氯苯那敏、美沙呋林和噻吩二胺单独存在时或亚硝化后均无致突变性。