Holliday R
Genetics Division, National Institute for Medical Research, London, Great Britain.
Mutat Res. 1987 Dec;181(2):215-7. doi: 10.1016/0027-5107(87)90098-4.
It is frequently assumed that DNA-damaging agents are carcinogenic because they induce mutations. However, another strong possibility is that the damage leads to heritable changes in the methylation of cytosine in DNA. Considerable evidence exists that gene expression in mammalian cells is in part controlled by methylation of specific DNA sequences. Carcinogens may act by altering the normal epigenetic controls of gene activity in specialised cells, and thereby produce aberrant heritable phenotypes. It is known that agents which inhibit DNA methylation can be carcinogenic and that tumour cells are altered in DNA methylation.
人们常常认为，DNA损伤剂具有致癌性是因为它们会诱发突变。然而，另一种可能性很大的情况是，这种损伤会导致DNA中胞嘧啶甲基化发生可遗传的变化。有大量证据表明，哺乳动物细胞中的基因表达部分受特定DNA序列甲基化的控制。致癌物可能通过改变特殊细胞中基因活性的正常表观遗传调控而起作用，从而产生异常的可遗传表型。已知抑制DNA甲基化的物质可能具有致癌性，而且肿瘤细胞的DNA甲基化会发生改变。
