Epigenetic changes and nontargeted radiation effects--is there a link?

It is now well accepted that the effects of ionizing radiation (IR) exposure can be noticed far beyond the borders of the directly irradiated tissue. IR can affect neighboring cells in the proximity, giving rise to a bystander effect. IR effects can also span several generations and influence the progeny of exposed parents, leading to transgeneration effects. Bystander and transgeneration IR effects are linked to the phenomenon of the IR-induced genome instability that manifests itself as chromosome aberrations, gene mutations, late cell death, and aneuploidy. While the occurrence of the above-mentioned phenomena is well documented, the exact mechanisms that lead to their development have still to be delineated. Evidence suggests that the IR-induced genome instability, bystander, and transgeneration effects may be epigenetically mediated. The epigenetic changes encompass DNA methylation, histone modification, and RNA-associated silencing. Recent studies demonstrated that IR exposure alters epigenetic parameters in the directly exposed tissues and in the distant bystander tissues. Transgeneration radiation effects were also proposed to be of an epigenetic nature. We will discuss the role of the epigenetic mechanisms in radiation responses, bystander effects, and transgeneration effects.