Wilson V L, Smith R A, Longoria J, Liotta M A, Harper C M, Harris C C
Proc Natl Acad Sci U S A. 1987 May;84(10):3298-301. doi: 10.1073/pnas.84.10.3298.
The genomic content of DNA 5-methyldeoxycytidine (m5dC) was measured in dividing normal human bronchial epithelial cells treated with a broad range of chemical carcinogens. At noncytotoxic concentrations, all of the carcinogenic agents tested significantly reduced cellular DNA m5dC content whereas the weakly carcinogenic and noncarcinogenic agents, benzo[e]pyrene and phenanthrene (respectively), did not. These reductions varied from 8% to 31% depending on the agent and the donor cells. The reductions in genomic m5dC levels were concentration dependent for the carcinogenic polycyclic aromatic hydrocarbon benzo[a]pyrene. We speculate that carcinogen-induced perturbation of DNA m5dC patterns may lead to heritable changes in gene expression and contribute to the molecular alterations involved in the initiation and the subsequent steps of the carcinogenesis process.
在使用多种化学致癌物处理的正常人类支气管上皮分裂细胞中，对DNA 5-甲基脱氧胞苷（m5dC）的基因组含量进行了测定。在无细胞毒性浓度下，所有测试的致癌剂均显著降低了细胞DNA的m5dC含量，而弱致癌剂和非致癌剂，即苯并[e]芘和菲（分别），则没有这种作用。这些降低幅度在8%至31%之间，具体取决于致癌物和供体细胞。致癌多环芳烃苯并[a]芘导致的基因组m5dC水平降低具有浓度依赖性。我们推测，致癌物诱导的DNA m5dC模式扰动可能导致基因表达的可遗传变化，并促成致癌过程起始及后续步骤中涉及的分子改变。
