DNA PRECURSOR POOL - A SIGNIFICANT TARGET FOR N-METHYL-N-NITROSOUREA IN C3H-10T1/2 CLONE 8 CELLS
DNA PRECURSOR POOL - A SIGNIFICANT TARGET FOR N-METHYL-N-NITROSOUREA IN C3H-10T1/2 CLONE 8 CELLS
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DOI：
10.1073/pnas.79.7.2211
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发表时间：
1982-01-01
期刊：
影响因子：
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通讯作者：
BAKER, MS
中科院分区：
文献类型：
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作者：
TOPAL, MD;BAKER, MS
在S期用无毒剂量的N-甲基-N-亚硝基脲体外处理同步化C3 H/10 T1/2克隆8 [小鼠]细胞。脱氧核糖核苷酸DNA前体池的色谱分离和每个细胞前体含量的测量显示，前体池中的核酸残基比DNA双链体中的残基对甲基化的敏感性高190- 13，000倍，这取决于甲基化的位点。这一结论来自于测量结果，例如，dATP中腺嘌呤的N-1位置的甲基化程度是DNA中相同位置的6.3倍，即使库中腺嘌呤含量仅为DNA螺旋中腺嘌呤含量的一小部分（0.0005）。DNA和DNA的相对敏感性随甲基化位点的不同而不同，顺序为腺嘌呤的N-1位>磷酸基>腺嘌呤的N-3位>鸟嘌呤的O-6位>鸟嘌呤的N-7位。这些结果的化学诱变和致癌的意义进行了讨论。
Synchronized C3H/10T1/2 clone 8 [mouse] 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 > phosphate > the N-3 position of adenine > the O6 position of guanine > the N-7 position of guanine. The significance of these results for chemical mutagenesis and carcinogenesis is discussed.