Oxidative stress, DNA methylation and carcinogenesis

Transformation of a normal cell to a malignant one requires phenotypic changes often associated with each of the initiation, promotion and progression phases of the carcinogenic process. Genes in each of these phases acquire alterations in their transcriptional activity that are associated either with hypermethylation-induced transcriptional repression (in the case of tumor suppressor genes) or hypomethylation-induced activation (in the case of oncogenes). Growing evidence supports a role of ROS-induced generation of oxidative stress in these epigenetic processes and as such we can hypothesize of potential mode(s) of action by which oxidative stress modulates epigenetic regulation of gene expression. This is of outmost importance given that various components of the epigenetic pathway and primarily aberrant DNA methylation patterns are used as potential biomarkers for cancer diagnosis and prognosis. (c) 2008 Elsevier Ireland Ltd. All rights reserved.