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Abstract：
1. In neutral aqueous solution N-methyl-N\'-nitro-N-nitrosoguanidine (MNNG) yields salts of nitrocyanamide as u.v.-absorbing products. With cysteine, as found independently by Schulz & McCalla (1969), the principal product is 2-nitràminothiazoline-4-carboxylic acid. Both these reactions liberate the methylating species; thiols enhance the rate markedly at neutral pH values. An alternative reaction with thiols gives cystine, presumably via the unstable S-nitrosocysteine. 2. Thiols (glutathione or N-acetylcysteine) in vitro at about the concentration found in mammalian cells enhance the rate of methylation of DNA markedly over that in neutral solution. 3. Treatment of cultured mammalian cells with MNNG results in rapid methylation of nucleic acids, the extent being greater the higher the thiol content of the cells. Rodent embryo cells are more extensively methylated than mouse L-cells of the same thiol content. Cellular thiol concentrations are decreased by MNNG. Proteins are less methylated by MNNG than are nucleic acids. 4. Methylation of cells by dimethyl sulphate does not depend on cellular thiol content and protein is not less methylated than nucleic acids. Methylation by MNNG may therefore be thiol-stimulated in cells. 5. Both in vitro and in cells about 7% of the methylation of DNA by MNNG occurs at the 6-oxygen atom of guanine. The major products 7-methylguanine and 3-methyladenine are given by both MNNG and dimethyl sulphate, but dimethyl sulphate does not yield O(6)-methylguanine. Possible reaction mechanisms to account for this difference between these methylating agents and its possible significance as a determinant of their biological effects are discussed.
摘要：
1.在中性水溶液中，N-甲基-N'-硝基-N-亚硝基胍（MNNG）产生硝基氰胺盐作为吸收u.v.的产物。有了半胱氨酸,由Schulz&McCalla(1969)独立发现，主要产物是2-硝胺噻唑啉-4-羧酸。这两种反应都释放出甲基化物质；硫醇在中性pH值下显着提高了速率。与硫醇的另一种反应产生胱氨酸，可能是通过不稳定的S-亚硝基半胱氨酸。2.硫醇（谷胱甘肽或N-乙酰半胱氨酸）在体外的浓度约为哺乳动物细胞中发现的浓度，与中性溶液相比，DNA的甲基化速率显着提高。3.用MNNG处理培养的哺乳动物细胞导致核酸的快速甲基化，程度越大,细胞的硫醇含量越高。啮齿动物胚胎细胞比相同巯基含量的小鼠L细胞更广泛地甲基化。MNNG降低了细胞硫醇浓度。蛋白质被MNNG甲基化的程度低于核酸。4.硫酸二甲酯对细胞的甲基化不取决于细胞硫醇含量，并且蛋白质的甲基化程度不比核酸低。因此,MNNG的甲基化可以在细胞中被硫醇刺激。5.在体外和细胞中，MNNG对DNA的甲基化中约有7％发生在鸟嘌呤的6-氧原子处。主要产物7-甲基鸟嘌呤和3-甲基腺嘌呤由MNNG和硫酸二甲酯提供，但是硫酸二甲酯不产生O（6）-甲基鸟嘌呤。讨论了解释这些甲基化剂之间这种差异的可能反应机理及其作为其生物学效应决定因素的可能意义。
