Sedgwick B, Robins P
Mol Gen Genet. 1980;180(1):85-90. doi: 10.1007/BF00267355.
A search has been made for mutants of E. coli that are constitutive for the adaptive response to alkylating agents. When selection was for resistance to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) the resulting strains all proved to be low in intracellular thiols. As MNNG has to be converted by thiols to the proximal mutagen methylnitrosamine, these strains were resistant simply because their low thiol levels made them less readily methylated by MNNG. The selection was therefore undertaken for strains resistant to N-methylnitrosourea (MNU) because this alkylating agent does not require activation by thiols. Four MNU resistant mutants proved to be constitutive for the adaptive response. Following exposure to (3H) MNNG, they showed the same low ratio of O6-methylguanine (O6MeG) to 7-methylguanine (7MeG) as adapted wild type bacteria. The ratio of 3-methyladenine (3MeA) to 7MeG was the same in the wild type, the adapted wild type, and the constitutive strains. When exposed to very high MNNG doses, the constitutive mutants were even more resistant to mutation and killing than the adapted wild type. They have an even greater ability than the adapted wild type to remove O6MeG from methylated DNA (Lindahl personal communication).
已对大肠杆菌中对烷化剂适应性反应呈组成型的突变体进行了搜索。当选择对N-甲基-N'-硝基-N-亚硝基胍(MNNG)具有抗性的菌株时,所有产生的菌株均被证明细胞内硫醇含量较低。由于MNNG必须由硫醇转化为近端诱变剂甲基亚硝胺,这些菌株具有抗性仅仅是因为它们低水平的硫醇使它们不易被MNNG甲基化。因此选择了对N-甲基亚硝基脲(MNU)具有抗性的菌株,因为这种烷化剂不需要硫醇激活。四个对MNU具有抗性的突变体被证明对适应性反应呈组成型。在暴露于(3H)MNNG后,它们显示出与适应的野生型细菌相同的低水平的O6-甲基鸟嘌呤(O6MeG)与7-甲基鸟嘌呤(7MeG)的比例。野生型、适应的野生型和组成型菌株中3-甲基腺嘌呤(3MeA)与7MeG的比例相同。当暴露于非常高剂量的MNNG时,组成型突变体比适应的野生型对突变和杀伤更具抗性。它们比适应的野生型具有更强的从甲基化DNA中去除O6MeG的能力(林达尔个人交流)。