Environmental Toxicant Exposure and Cancer: the Role of Epigenetic Changes and Protection by Phytochemicals.

Exposure to environmental toxicants is a well-documented predisposing factor for cancer. Although genetic alterations have long been known to occur through exposure to some environmental carcinogens, there is another layer of genome regulatory system named epigenetic system. Epigenetics is defined as any reversible and heritable change in cellular patterns of gene expression that does not alter DNA sequence. This layer of gene control plays a key role in early stages of carcinogenesis by reprogramming cells to what is known as cancer stem cells, a process with great similarities to somatic cell reprogramming into "induced pluripotent stem cell". Environmental toxicants could directly promote carcinogenesis through disturbing promoter CpG island hypermethylation, and silencing of tumor suppressor genes, hypomethylation of transposable elements and genomic instability induced by environmental toxicants. Environmental toxicants could also indirectly affect epigenetic programming of nucleus through inducing inflammatory signaling pathways that converge on NF-κB or STAT3 activation. Considering the reversibility of epigenetic alterations and their pivotal role in early carcinogenesis, reversion of these alterations could be a promising approach for chemoprevention. Selected phytochemicals have shown desirable effects through regulation of the most important epigenetic mechanisms including DNA methylation, histone modifications and microRNA expression, as well as modulation of SIRT-1 and STAT-3 signaling pathways. The present review aims to outline the epigenetic mechanisms underlying carcinogenic effects of environmental toxicants, and the protective effects of phytochemicals in reversing epigenetic aberrations in the regulatory pathways steering normal cell homeostasis.