Ruiz-Laguna J, Prieto-Alamo M J, Pueyo C
Departamento de Bioquímica y Biología Molecular, Universidad de Córdoba, Córdoba, Spain.
Environ Mol Mutagen. 2000;35(1):22-30. doi: 10.1002/(sici)1098-2280(2000)35:1<22::aid-em4>3.0.co;2-x.
Escherichia coli strains with different combinations of null mutations in the katG, katE, sodA, sodB, fpg, and mutY genes were constructed to compare their spontaneous mutation frequencies and sensitivities to various oxidants with those of bacteria solely deficient in catalase (katG katE) or cytosolic superoxide dismutase (sodA sodB) and the parental strain possessing a full complement of these enzymes. The MutY DNA glycosylase represented the major protection against the mutagenic consequences of processes associated with normal aerobic metabolism. Spontaneous mutagenesis in MutY-lacking bacteria was not influenced by the absence of (A)BC excinuclease or the presence of MucAB proteins, a result consistent with 8-oxoguanine being a principal premutational lesion. In contrast, catalase and SOD represented the major protection against the genotoxic consequences of bursts of oxidative stress caused by reactive-oxygen-generating compounds. Therefore, only bacteria simultaneously defective in both katG and katE or sodA and sodB genes were hypersensitive with respect to mutability by peroxide and superoxide, respectively. These data suggest that oxidative lesions other than 8-oxoguanine contribute to mutagenesis by hydrogen peroxide and redox-cycling chemicals.
构建了在katG、katE、sodA、sodB、fpg和mutY基因中具有不同组合无效突变的大肠杆菌菌株，以比较它们与仅缺乏过氧化氢酶（katG katE）或胞质超氧化物歧化酶（sodA sodB）的细菌以及拥有这些酶完整互补的亲本菌株相比的自发突变频率和对各种氧化剂的敏感性。MutY DNA糖基化酶是对与正常有氧代谢相关过程的诱变后果的主要保护。缺乏MutY的细菌中的自发诱变不受（A）BC核酸外切酶的缺失或MucAB蛋白的存在的影响，这一结果与8-氧鸟嘌呤是主要的前突变损伤一致。相比之下，过氧化氢酶和超氧化物歧化酶是对由活性氧生成化合物引起的氧化应激爆发的遗传毒性后果的主要保护。因此，只有同时在katG和katE基因或sodA和sodB基因中存在缺陷的细菌分别对过氧化物和超氧化物的诱变敏感性过高。这些数据表明，除8-氧鸟嘌呤外的氧化损伤也会导致过氧化氢和氧化还原循环化学物质引起的诱变。
