Ionizing radiation-induced oxidative stress, epigenetic changes and genomic instability: the pivotal role of mitochondria

Int J Radiat Biol. 2015 Jan;91(1):1-12. doi: 10.3109/09553002.2014.934929.


Purpose: To review the data concerning the role of endogenously generated reactive oxygen species (ROS) in the non-targeted ionizing radiation (IR) effects and in determination of the cell population's fate, both early after exposure and after many generations.

Conclusions: The short-term as well as chronic oxidative stress responses mainly are produced due to ROS generation by the electron transport chain (ETC) of the mitochondria and by the cytoplasmic NADPH oxidases. Whether the induction of the oxidative stress and its consequences occur or are hampered in a single cell largely depends on the interaction between the nucleus and the cellular population of several hundred or thousands of mitochondria that are genetically heterogeneous. High intra-mitochondrial ROS level is damaging the mitochondrial (mt) DNA and its mutations affect the epigenetic control mechanisms of the nuclear (n) DNA, by decreasing the activity of methyltransferases and thus, causing global DNA hypomethylation. These changes are transmitted to the progeny of the irradiated cells. The chronic oxidative stress is the main cause of the late post-radiation effects, including cancer, and this makes it an important adverse effect of exposure to IR and a target for radiological protection.

Keywords: Ionizing radiation; carcinogenesis; epigenetics; genomic instability; mitochondrion; oxidative stress; reactive oxygen/nitrogen species.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carcinogenesis / radiation effects
  • Epigenesis, Genetic / radiation effects*
  • Genomic Instability / radiation effects*
  • Humans
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Mitochondria / radiation effects*
  • Oxidative Stress / radiation effects*
  • Reactive Oxygen Species / metabolism


  • Reactive Oxygen Species