Role of epigenetics in tumor induction by non-genotoxic carcinogens

Non-genotoxic carcinogens are chemicals that cause the development of tumors through the indirect induction of neoplastic transformation without altering the DNA sequence. The mechanisms of non-genotoxic carcinogenesis are very complex and there is no common mode-of-action that characterizes all non-genotoxic carcinogens making detection of these carcinogens difficult. Recently, epigenetic alterations have been suggested as key cancer-related events induced by non-genotoxic carcinogens. The goal of this minireview is to summarize current knowledge on the similarities and differences in epigenetic changes induced by known non-genotoxic carcinogens, such as phenobarbital, WY-14,643, arsenic, methapyrilene, nickel and 2,3,7,8-tetrachlorodibenzo-p-dioxin, and estimate a potential of using these findings to establish assays for carcinogens detection with non-genotoxic characteristics. This minireview highlights alterations in DNA methylation, histone modifications, and changes in microRNAs as the promising epigenetic mechanisms with respect to carcinogenic potential assessment of non-genotoxic chemicals. The understanding of epigenetic mechanisms during carcinogenesis induced by non-genotoxic carcinogens may help identify new biomarkers for the evaluation of carcinogenic potential of non-genotoxic carcinogens and may contribute to human health risk assessment.