Friedrich U, Coffino P
Proc Natl Acad Sci U S A. 1977 Feb;74(2):679-83. doi: 10.1073/pnas.74.2.679.
The effects of mutagens on three genetic markers--resistance to ouabain, 6-thioguanine, and dibutyryl cyclic AMP (Bt2cAMP), were investigated in a mouse lymphoma cell line, S49. Nitrosoguanidine, ethyl methanesulfonate, ICR 191, and x-rays were used. Mutagen-specific responses were seen. Ouabain resistance was induced by nitrosoguanidine, but not by ICR 191. ICR 191 induced resistance to 6-thioguanine more efficiently than did nitrosoguanidine; the converse was true of resistance to Bt2cAMP. The relative frequency of biochemically distinguishable subtypes of mutants resistant to Bt2cAMP was characteristic of the mutagen used to generate them. The results can be interpreted as follows: nitrosoguanidine and ethyl methanesulfonate frequently, but ICR 191 and x-rays rarely, give rise to DNA base sequence changes that result in structurally altered but functional proteins. This type of change is required for induction of mutants resistant to ouabain and of certain classes of mutants resistant to Bt2cAMP. Resistance to 6-thioguanine and other classes of mutants resistant to Bt2cAMP can result from DNA base sequence changes that lead to extensive alteration of protein structure or expression; these changes are induced by ICR 191 or x-rays.
在小鼠淋巴瘤细胞系S49中,研究了诱变剂对三种遗传标记物——哇巴因抗性、6-硫鸟嘌呤抗性和二丁酰环磷腺苷(Bt2cAMP)的影响。使用了亚硝基胍、甲磺酸乙酯、ICR 191和X射线。观察到了诱变剂特异性反应。亚硝基胍可诱导哇巴因抗性,但ICR 191不能。ICR 191诱导6-硫鸟嘌呤抗性的效率高于亚硝基胍;对Bt2cAMP的抗性则相反。对Bt2cAMP有抗性的突变体生化可区分亚型的相对频率是用于产生它们的诱变剂所特有的。结果可解释如下:亚硝基胍和甲磺酸乙酯经常,但ICR 191和X射线很少,引起DNA碱基序列变化,导致结构改变但功能正常的蛋白质。诱导对哇巴因有抗性的突变体和某些类别的对Bt2cAMP有抗性的突变体需要这种类型的变化。对6-硫鸟嘌呤的抗性和其他类别的对Bt2cAMP有抗性的突变体可能源于DNA碱基序列变化,导致蛋白质结构或表达的广泛改变;这些变化由ICR 191或X射线诱导。