The Role of Dna Methylation in Cancer

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This chapter discusses the role of DNA methylation in carcinogenesis and tumor diversification. The methylation of HpaII and Hha1 sites in DNA isolated from the normal rat livers and from transplantable hepatomas shows that the Hha1 sites in the Ī±-fetoprotein genes are less methylated in hepatoma cell DNA than in the liver DNA. A decreased methylation of the CCGG sequences in the rat hepatoma DNA than in the normal rat livers is also observed. There are two corollaries to the hypothesis that chemical carcinogens act in part by inhibiting the DNA methylation: first, chemical carcinogens should be able to activate nonexpressed genes in suitable selectable systems in a similar manner to that of 5-Aza-CR, and second, agents that inhibit methylation such as 5-Aza-CR should be carcinogenic. The methylation of poly dCā€“dG with ethyl methane sulfonate (EMS) stimulates the methyl-accepting ability of the DNA by rat DNA methyltransferase. Thus, carcinogens can have multiple effects on DNA methylation, acting either to decrease or to increase methylation, depending on the specific lesion induced in DNA.

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