Lethal and Mutagenic Lesions Produced in DNA by Exposure to X-Rays and Activi Oxygen Species

1.泥噬菌体被用来分离至少四个基因融合的lacZ基因（α：：lacZ，超氧化物诱导的），诱导处理与超氧化物发生剂，如甲基紫精（百草枯）和甲萘醌。半乳糖苷酶的诱导在这些融合菌株与超氧自由基产生剂需要有氧代谢。氧合过度（i.例如，用氧气鼓泡培养物）也诱导融合。另一方面，过氧化氢在已知引起适应性反应的浓度下不会诱导融合。引入oxyr、htpr或reca突变不影响诱导。三个融合菌株表现出增加的敏感性甲基紫精，但不过氧化氢。所有这些融合都位于大肠杆菌染色体的6- 36-min区域。有人还发现，某些膜桥接药物（麻醉剂），干扰膜结合呼吸活动诱导锰超氧化物歧化酶只有在有氧条件下。结果表明，这些膜结合药物的作用破坏了细胞膜的电子传递系统，从而产生超氧阴离子.实验表明，E.大肠杆菌对X射线和过氧化氢的致突变作用敏感性增加，表明DNA中产生的胸腺嘧啶二醇和AP位点是细菌细胞的主要致突变前损伤。还发现8-羟基鸟嘌呤也是预致突变的，并且是GC-TA颠换的原因。

1. Mud phage was used to isolate at least four gene fusions to the lacZ gene(soi : : lacZ, soi for superoxide inducible)that were induced by treatment with superoxide generators such as methyl viologen(paraquat)and menadione. The induction of -galactosidase in these fusion strains with the superoxide radical generating agents required aerobic metabolism. Hyperoxygenation(i. e., bubbling of cultures with oxygen gas)also induced the fusions. On the other hand, hydrogen peroxide did not induce the fusions at concentrations that are known to invoke an adaptive response. Introduction of oxyr, htpr or reca mutations did not affect the induction. Three of the fusion strains exhibited increased sensitivity to methyl viologen but not to hydrogen peroxide. All these fusions were located in the 6- to 36-min region of the Escherichia coli chromosome.2. It was also found that certain membrane-briding drugs(anesthetics)which disturb the membrane-bound respiratory activity induce Mn-superoxide dismutase only under aerobic conditions. The results suggested that such membrane-binding drugs generate superoxide as a result of disruption of the electron transport system of the membrane by the action of the drugs.3. The experiments revealed that nth and xthnfo mutants of E. coli showed increased sensitivity to mutagenic effect of X-rays and hydrogen peroxide, indicating that thymine glycols and AP sites produced in DNA were a main premutagenic lesion in bacterial cells. It was also found that 8-hydroxy-guanine was also premutagenic and a cause for GC-TA transversion.