DNA Methylation at the C-5 Position of Cytosine by a Methyl Radical: A Link between Environmental Agents and Epigenetic Change

Abstract

Methylation of the cytosine C-5 position in the promoter region of tumor suppressor genes is an important mechanism of carcinogenesis in addition to gene mutation. However, the actual mechanisms of de novo methylation in relation to environmental agents are not clear. We found that cytosine C-5 methylation occurred in the monomer nucleoside and DNA by various methyl radical generating systems, including environmental agents. The possible role of this radical-induced DNA methylation in carcinogenesis is discussed in connection with the presently accepted concept of cancer epigenetics.