Weitzman S A, Turk P W, Milkowski D H, Kozlowski K
Department of Medicine, Northwestern University Medical School, Chicago, IL 60611.
Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1261-4. doi: 10.1073/pnas.91.4.1261.
Methylation of cytosines in DNA is important for the regulation of expression of many genes. During carcinogenesis, normal patterns of gene methylation can be altered. Oxygen radical injury, shown to damage DNA in a variety of ways associated with cancer development and other conditions, has been suggested to affect DNA methylation, but a mechanism has not been demonstrated. Using oligonucleotides containing the common oxygen radical adduct 8-hydroxyguanine to replace guanine, we found that the enzymatic methylation of adjacent cytosines is profoundly altered. Furthermore, there is a high degree of positional specificity with respect to this effect. Thus, free radical injury may explain some of the altered methylation observed during carcinogenesis.
DNA中胞嘧啶的甲基化对于许多基因表达的调控至关重要。在致癌过程中，正常的基因甲基化模式可能会发生改变。氧自由基损伤已被证明会以多种与癌症发展及其他病症相关的方式破坏DNA，有人提出它会影响DNA甲基化，但尚未证实其机制。我们使用含有常见氧自由基加合物8-羟基鸟嘌呤的寡核苷酸来取代鸟嘌呤，发现相邻胞嘧啶的酶促甲基化发生了深刻改变。此外，这种效应具有高度的位置特异性。因此，自由基损伤可能解释了致癌过程中观察到的一些甲基化改变现象。
