Non-targeted radiation effects—An epigenetic connection

Ionizing radiation (IR) is a pivotal diagnostic and treatment modality, yet it is also a potent genotoxic agent that causes genome instability and carcinogenesis. While modern cancer radiation therapy has led to increased patient survival rates, the risk of radiation treatment-related complications is becoming a growing problem. IR-induced genome instability has been well-documented in directly exposed cells and organisms. It has also been observed in distant ‘bystander’ cells. Enigmatically, increased instability is even observed in progeny of pre-conceptually exposed animals, including humans. The mechanisms by which it arises remain obscure and, recently, they have been proposed to be epigenetic in nature. Three major epigenetic phenomena include DNA methylation, histone modifications and small RNA-mediated silencing. This review focuses on the role of DNA methylation and small RNAs in directly exposed and bystander tissues and in IR-induced transgenerational effects. Here, we present evidence that IR-mediated effects are maintained by epigenetic mechanisms.