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

暴露于 X 射线和活性氧在 DNA 中产生致命和诱变损伤

基本信息

批准号：
02680168
负责人：
YONEI Shuji
金额：
$ 1.28万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02680168/
关键词：
Active oxygen spesies X-rays Oxidative DNA damage DNA repair Adaptive response Gene expression Mutagenesis DNA損傷 oxyR遺伝子遺伝子発現誘導 sodA遺伝子突然変異原性

项目摘要

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.

1。使用泥浆噬菌体将至少四个基因融合分离为LACZ基因（SOI ：： lacz，用于超氧化物诱导的SOI），这些基因是通过用超氧化物发电机（例如甲基Viologen（Paraquat）和Menadione处理的，诱导的超氧化物诱导的）。在这些融合菌株中与超氧化物自由基产生剂的诱导 - 半乳糖苷酶需要有氧代谢。高氧（即，氧气培养物的冒泡）也诱导了融合。另一方面，过氧化氢不会以已知会引起自适应反应的浓度诱导融合。 oxyr，HTPR或RECA突变的引入不会影响诱导。三个融合菌株对甲基毒素剂的敏感性增加，但对过氧化氢的敏感性不高。所有这些融合都位于大肠杆菌染色体的6至36分钟区域。2。还发现，仅在有氧条件下，膜结合的呼吸活性会诱导膜结合的呼吸活性的某些膜构型药物（麻醉药）。结果表明，这种膜结合药物通过药物的作用破坏了膜的电子传输系统，从而产生超氧化物。3。实验表明，大肠杆菌的nth和XTHNFO突变体对X射线和过氧化氢的诱变作用的敏感性增加，表明在DNA中产生的胸腺嘧啶甘油和AP位点是细菌细胞中主要的前食病变。还发现8-羟基甘瓜也是前毒素的，并且是GC-TA转移的原因。