The mutagenic mechanism of oxygenated alkylhydrazones occurs through alkyl radicals and alkyldiazonium ions
The mutagenic mechanism of oxygenated alkylhydrazones occurs through alkyl radicals and alkyldiazonium ions
复制标题
氧化烷基腙的诱变机制是通过烷基自由基和烷基重氮离子发生的
DOI：
10.1039/c6tx00430j
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发表时间：
2017
影响因子：
2.1
通讯作者：
M. Mochizuki
中科院分区：
文献类型：
--
作者：
K. Inami;M. Takada;M. Nagata;T. Higashi;M. Mochizuki
据报道，丙酮烷基腙在鼠伤寒沙门氏菌ta1535暴露于氧后具有致突变性，其结果是通过自氧化形成相应的2-烷基偶氮-2-丙基氢过氧化物。本研究通过比较甲基类似物2-甲基偶氮-2-丙基过氧化氢（MAPH）对沙门氏菌的致突变性，检测致突变性的DNA加合物，并利用电子自旋共振（ESR）自旋捕获法观察羟自由基和甲基自由基，探讨MAPH的致突变性机制。对羟基自由基敏感的鼠伤寒沙门菌yg3001和对烷基化剂敏感的鼠伤寒沙门菌yg7108均表现出较强的诱变性。此外，MAPH与DNA反应生成8-羟基-2 ' -脱氧鸟苷和do6 -甲基-2 ' -脱氧鸟苷。这些结果表明，腙的致突变性归因于自氧化产生的活性物质，即烷基重氮离子和羟基自由基。
Acetone alkylhydrazones have been reported to be mutagenic inSalmonella typhimuriumTA1535 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 specificSalmonellastrains, 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 bothSalmonella typhimuriumYG3001, a strain sensitive to hydroxyl radicals, andSalmonella typhimuriumYG7108, a strain sensitive to alkylating agents, than the originalSalmonella typhimuriumTA1535 strain. Moreover, MAPH resulted in the formation of 8-hydroxy-2′-deoxyguanosine andO6-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.