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

1. 用泥噬菌体分离了至少4个与lacZ基因融合的基因（soi:: lacZ, soi for superoxide inducible），这些基因是用过氧化物产生剂如甲基紫草枯（百草枯）和甲醌处理后诱导的。在这些融合菌株中用超氧自由基生成剂诱导-半乳糖苷酶需要有氧代谢。Hyperoxygenation(我。（例如，用氧气使培养物冒泡）也引起了融合。另一方面，过氧化氢没有在已知的浓度下引起适应性反应的融合。引入oxyr、htpr或reca突变对诱导不产生影响。其中三个融合菌株对甲基紫菌素的敏感性增加，但对过氧化氢的敏感性没有增加。所有这些融合体均位于大肠杆菌染色体的6 ~ 36min区域2。还发现，某些干扰膜结合呼吸活动的膜桥药（麻醉剂）仅在有氧条件下才诱导mn超氧化物歧化酶。结果表明，这类膜结合药物是由于其作用破坏了膜的电子传递系统而产生超氧化物的。实验发现，大肠杆菌的n和xthnfo突变体对x射线和过氧化氢的致突变作用的敏感性增加，表明胸腺嘧啶二醇和DNA中产生的AP位点是细菌细胞的主要致突变前病变。还发现8-羟基鸟嘌呤也具有前诱变性，是导致GC-TA翻转的原因之一。

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.