Resistance of Salmonella typhimurium TA 1535 to O6-guanine methylation and mutagenesis induced by low doses of N-methyl-N'-nitro-N-nitrosoguanidine: an apparent constitutive repair activity.
Resistance of Salmonella typhimurium TA 1535 to O6-guanine methylation and mutagenesis induced by low doses of N-methyl-N'-nitro-N-nitrosoguanidine: an apparent constitutive repair activity.
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鼠伤寒沙门氏菌 TA 1535 对低剂量 N-甲基-N-硝基-N-亚硝基胍诱导的 O6-鸟嘌呤甲基化和诱变的抗性：明显的组成性修复活性。
DOI：
10.1093/carcin/3.3.327
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发表时间：
1982
期刊：
影响因子：
4.7
通讯作者：
S. Milstein
中科院分区：
文献类型：
--
作者：
J. Guttenplan;S. Milstein
通过碱基对置换诱变剂回复的沙门氏菌试验菌株对N-甲基-N-亚硝基化合物的诱变作用相对不敏感。这种不敏感性的一个原因是这些菌株在对这些化合物的致突变作用敏感之前能够承受低剂量的这些化合物。本报告表明，用N-甲基-N '-硝基-N-亚硝基胍（MNNG）在缓冲液中处理鼠伤寒沙门氏菌TA 1535诱导的诱变是双相的，在低剂量时有一个低灵敏度范围，几乎不发生诱变，然后是一个高灵敏度范围，在超过表观阈值剂量后开始发生。从细菌中提取的DNA中O 6-甲基鸟嘌呤（O 6-MeG）的水平遵循类似的剂量-反应曲线，表明诱变对O 6-MeG的依赖性。相反，DNA中7-甲基鸟嘌呤（7-MeG）的水平随剂量线性增加。在最低剂量的MNNG下，O 6-MeG检测不到，而7-MeG很容易检测到。虽然这种对O 6-烷基化的抗性已经在MNNG预处理的（适应的）E.在未经预处理的细胞中未见报道。然后用MNNG处理DNA，观察到O_6-MeG的产生呈线性剂量反应。在低剂量后从MNNG处理的细胞中分离的DNA中缺乏O 6-MeG归因于细菌中的可饱和的组成型修复活性。在暴露于短剂量的N-亚硝基-N-甲基脲（NMU），随后在缓冲液中孵育后，试图观察O 6-MeG从细菌中的去除是不成功的，可能是因为所有的修复都发生在处理和裂解细胞所需的时间内。
Salmonella tester strains which are reverted by base-pair substitution mutagens are relatively insensitive to the mutagenic effects of N-methyl-N-nitroso compounds. One reason for this insensitivity is the ability of these strains to withstand low doses of these compounds before they become sensitive to their mutagenic effects. In this report it is shown that mutagenesis induced by treatment of Salmonella typhimurium TA 1535 with N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) in buffer is biphasic with a low sensitivity range at low doses where little mutagenesis occurs, followed by a high sensitivity range whose onset begins after an apparent threshold dose has been exceeded. levels of O6-methylguanine (O6-MeG) in the DNA extracted from the bacteria follow a similar dose-response curve suggesting a dependency of mutagenesis on O6-MeG. In contrast, levels of 7-methylguanine (7-MeG) in the DNA increase linearly with dose. O6-MeG was undetectable at the lowest dose of MNNG whereas 7-MeG was readily detectable. Although such resistance to O6-alkylation has been demonstrated in MNNG- pretreated (adapted) E. coli, it has not been reported in unpretreated cells. Then isolated DNA was treated with MNNG a linear dose-response in the generation of O6-MeG was observed. The lack of O6-MeG in DNA isolated from MNNG treated cells after low doses is attributed to a saturable, constitutive repair activity in the bacteria. An attempt to observe the removal of O6-MeG from the bacteria after exposure to a short challenge dose of N-nitroso-N-methylurea (NMU) followed by a subsequent incubation in buffer was unsuccessful, probably because all the repair occurred within the time necessary to treat and lyse the cells.