Epigenetics meets radiation biology as a new approach in cancer treatment

Abstract

Cancer is a disease that results from both genetic and epigenetic changes. In recent decades, a number of people have investigated the disparities in gene expression resulting from variable DNA methylation alteration and chromatin structure modification in response to the environment. Especially, colon cancer is a great model system for investigating the epigenetic mechanism for aberrant gene expression alteration. Ionizing radiation (IR) could affect a variety of processes within exposed cells and, in particular, cause changes in gene expression, disruption of cell cycle arrest, and apoptotic cell death. Even though there is growing evidence on the importance of epigenetics and biological processes induced by radiation exposure in various cancer types including colon cancer, specific epigenetic alterations induced by radiation at the molecular level are incompletely defined. This review focuses on discussing possible IR-mediated changes of DNA methylation and histone modification in cancer.

Figure 1

Radiation effect on DNA methylation. The schematic shows the change of global DNA methylation by radiation exposure in a cancer system. Radiation might induce global DNA hypomethylation through a decrease in DNA methyltransferases, including DNMT1, DNMT3a, DNMT 3b, and MeCP2. This phenomenon results in genomic instability in cancer.

Figure 2

Radiation effect on histones. Radiation can induce phosphorylation of histone H2AX, and trimethylation of histone H4K20, which affect gene expression patterns, consequently leading to cell death, changes in cell cycle, and genomic instability. These events may be closely related to the therapeutic, protective, or detrimental response to irradiation.