Inami Keiko, Takada Miki, Nagata Miho, Higashi Toshinori, Mochizuki Masataka
Faculty of Pharmaceutical Sciences , Tokyo University of Science , 2641 Yamazaki , Noda-shi , Chiba 278-8510 , Japan . Email:
Kyoritsu University of Pharmacy , Shibakoen1-5-30 , Minato-ku , Tokyo 105-8512 , Japan.
Toxicol Res (Camb). 2017 Feb 2;6(2):173-178. doi: 10.1039/c6tx00430j. eCollection 2017 Mar 1.
Acetone alkylhydrazones have been reported to be mutagenic in TA1535 after exposure to oxygen, and the corresponding 2-alkylazo-2-propyl hydroperoxides are formed by autoxidation as a result. The aims of this study were to investigate the mutagenic mechanisms of a methyl analogue, 2-methylazo-2-propyl hydroperoxide (MAPH), by comparing the mutagenic potency of specific strains, detecting the DNA adducts that cause mutagenicity, and observing the hydroxyl radical and methyl radical with the electron spin resonance (ESR) spin-trapping method. MAPH showed stronger mutagenicity in both YG3001, a strain sensitive to hydroxyl radicals, and YG7108, a strain sensitive to alkylating agents, than the original TA1535 strain. Moreover, MAPH resulted in the formation of 8-hydroxy-2'-deoxyguanosine and -methyl-2'-deoxyguanosine in a reaction with DNA. These results showed that the mutagenicity of hydrazones was ascribed to the generation of reactive species by autoxidation, namely that of the alkyldiazonium ion and also the hydroxyl radical.
据报道，丙酮烷基腙在暴露于氧气后对TA1535具有致突变性，相应的2-烷基偶氮-2-丙基氢过氧化物通过自氧化作用形成。本研究的目的是通过比较特定菌株的致突变能力、检测导致致突变性的DNA加合物以及用电子自旋共振（ESR）自旋捕获法观察羟基自由基和甲基自由基，来研究甲基类似物2-甲基偶氮-2-丙基氢过氧化物（MAPH）的致突变机制。与原始的TA1535菌株相比，MAPH在对羟基自由基敏感的YG3001菌株和对烷基化剂敏感的YG7108菌株中均表现出更强的致突变性。此外，MAPH与DNA反应时会导致8-羟基-2'-脱氧鸟苷和N-甲基-2'-脱氧鸟苷的形成。这些结果表明，腙的致突变性归因于自氧化产生的活性物种，即烷基重氮离子和羟基自由基。
