DNA前体池：N-甲基-N-亚硝基脲在C3H/10T1/2克隆8细胞中的一个重要靶点。
DNA precursor pool: a significant target for N-methyl-N-nitrosourea in C3H/10T1/2 clone 8 cells.
作者信息
Topal M D, Baker M S
出版信息
Proc Natl Acad Sci U S A. 1982 Apr;79(7):2211-5. doi: 10.1073/pnas.79.7.2211.
Abstract
Synchronized C3H/10T1/2 clone 8 cells were treated in vitro with a nontoxic dose of N-methyl-N-nitrosourea during their S phase. Chromatographic isolation of the deoxyribonucleotide DNA precursor pool and measurement of the precursor content per cell showed that a nucleic acid residue in the precursor pool is 190-13,000 times more susceptible to methylation than a residue in the DNA duplex, depending on the site of methylation. This conclusion comes from measurements indicating that, for example, the N-1 position of adenine in dATP is 6.3 times more methylated than the same position in the DNA, even though the adenine content of the pool is only a fraction (0.0005) of the adenine content of the DNA helix. The comparative susceptibility between pool and DNA was found to vary with the site of methylation in the order the N-1 position of adenine greater than phosphate greater than the N-3 position of adenine greater than the O6 position of guanine greater than the N-7 position of guanine. The significance of these results for chemical mutagenesis and carcinogenesis is discussed.
摘要
在同步化的C3H/10T1/2克隆8细胞处于S期时，用无毒剂量的N-甲基-N-亚硝基脲进行体外处理。对脱氧核糖核苷酸DNA前体库进行色谱分离并测量每个细胞的前体含量，结果表明，前体库中的核酸残基比DNA双链中的残基对甲基化的敏感性高190 - 13000倍，这取决于甲基化位点。这一结论来自于测量结果，例如，dATP中腺嘌呤的N-1位甲基化程度比DNA中相同位置高6.3倍，尽管前体库中腺嘌呤的含量仅为DNA螺旋中腺嘌呤含量的一小部分（0.0005）。发现前体库与DNA之间的相对敏感性随甲基化位点的不同而变化，顺序为：腺嘌呤的N-1位＞磷酸＞腺嘌呤的N-3位＞鸟嘌呤的O6位＞鸟嘌呤的N-7位。讨论了这些结果对化学诱变和致癌作用的意义。
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