Milligan J R, Skotnicki S, Lu S J, Archer M C
Department of Medical Biophysics, University of Toronto, Ontario Cancer Institute, Canada.
IARC Sci Publ. 1991(105):329-31.
A sequencing assay was used to determine the reactivity of N-nitroso compounds that are simple methylating agents with individual nucleotides in a defined DNA sequence. The maximal difference in reactivity between guanines is about five fold. DNA in the Z, cruciform and H conformations was shown to be methylated by N-methyl-N-nitrosourea in a manner which was indistinguishable from the reactivity of B-DNA. Electronic factors rather than steric factors appear to dominate the methylation reaction. Transcriptionally active genes were shown to be methylated by N-nitroso compounds in vivo more extensively than untranscribed genes. The results suggest that local sequence, secondary conformation and transcriptional activity may all influence the carcinogenic potential of N-nitroso compounds.
采用测序分析方法来测定作为简单甲基化剂的N-亚硝基化合物与特定DNA序列中单个核苷酸的反应活性。鸟嘌呤之间反应活性的最大差异约为五倍。研究表明，Z型、十字形和H型构象的DNA被N-甲基-N-亚硝基脲甲基化的方式与B-DNA的反应活性无法区分。电子因素而非空间因素似乎主导了甲基化反应。体内研究显示，与未转录基因相比，转录活性基因被N-亚硝基化合物甲基化的程度更高。结果表明，局部序列、二级构象和转录活性可能都会影响N-亚硝基化合物的致癌潜力。
