Inflammation-mediated cytosine damage : A mechanistic link between inflammation and the epigenetic alterations in human cancers

Aberrant methylation patterns have long been known to exist in the promoter regions of key regulatory genes in the DNA of tumor cells. However, the mechanisms by which these methylation patterns become altered during the transformation of normal cells to tumor cells have remained elusive. We have recently shown in in vitro studies that inflammation-mediated halogenated cytosine damage products can mimic 5-methylcytosine in directing enzymatic DNA methylation and in enhancing the binding of methyl-binding proteins whereas certain oxidative damage products inhibit both. We have therefore proposed that cytosine damage products could potentially interfere with normal epigenetic control by altering DNA-protein interactions critical for gene regulation and the heritable transmission of methylation patterns. These inflammation-mediated cytosine damage products may provide, in some cases, a mechanistic link between inflammation and cancer.