Transgenerational Radiation Epigenetics

Abstract

Abstract : The carcinogenic effects of low dose radiation are not clear. Moreover, it is not known if exposure to low dose radiation increases cancer risk in offspring of irradiated parents. Radiation is known to damage DNA and cause mutations. Cancer arises in part through mutations in oncogenes and tumor suppressor genes. However, epigenetics is also known to play an important and perhaps central role in cancer induction. Epigenetics is here defined as a heritable change in phenotype without an underlying mutational event. Epigenetic alterations may be induced early in development as a result of diet or environmental exposure. These alterations can persist into adulthood, and may increase the risk of developing diseases such as cancer later in life. Radiation has been shown to cause epigenetic effects in mammalian cells and in mice, although the role of these in human cancer is entirely unknown. Here we hypothesize that the carcinogenic effect of radiation may in part be due to epigenetic alterations. In this study we will determine if early exposure to radiation leads to a change in DNA methylation in adult tissues and in ensuing unexposed generations, and if these changes correlate with increased cancer susceptibility. We also expect to identify a radiation exposure signature which when validated, could be used clinically as a biomarker of radiation exposure. These experiments will also open up new avenues of investigation into the role of epigenetics in cancer caused by radiation and other environmental carcinogens.