Involvement of reactive oxygen species (ROS) in the induction of genetic instability by radiation

J Radiat Res. 2004 Jun;45(2):181-8. doi: 10.1269/jrr.45.181.

Abstract

Radiation generates reactive oxygen species (ROS) that interact with cellular molecules, including DNA, lipids, and proteins. To know how ROS contribute to the induction of genetic instability, we examined the effect of the anti-ROS condition, using both ascorbic acid phosphate (APM) treatment or a low oxygen condition, on the induction of delayed reproductive cell death and delayed chromosome aberrations. The primary surviving colonies of mouse m5S-derived cl. 2011-14 cells irradiated with 6 Gy of X-rays were replated and allowed to form secondary colonies. The anti-ROS treatments were applied to either preirradiation culture or postirradiation cultures for primary or secondary colony formation. Both anti-ROS conditions relieved X-ray-induced acute cell killing to a similar extent. These anti-ROS conditions also relieved genetic instability when those conditions were applied during primary colony formation. However, no effect was observed when the conditions were applied during preirradiation culture and secondary colony formation. We also demonstrated that the amounts of ROS in X-ray-irradiated cells rapidly increase and then decrease at 6 hr postirradiation, and the levels of ROS then gradually decrease to a baseline within 2 weeks. The APM treatment kept the ROS production at a lower level than an untreated control. These results suggest that the cause of genetic instability might be fixed by ROS during a 2-week postirradiation period.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Ascorbic Acid / analogs & derivatives*
  • Ascorbic Acid / pharmacology*
  • Cell Hypoxia / drug effects
  • Cell Hypoxia / physiology
  • Cell Hypoxia / radiation effects
  • Cell Line
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Chromosome Aberrations / drug effects
  • Chromosome Aberrations / radiation effects
  • Chromosomes, Human, Pair 11 / drug effects*
  • Chromosomes, Human, Pair 11 / radiation effects*
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Genomic Instability / drug effects*
  • Genomic Instability / radiation effects*
  • Humans
  • Mice
  • Oxygen / metabolism*
  • Reactive Oxygen Species / metabolism*
  • X-Rays

Substances

  • Reactive Oxygen Species
  • ascorbate-2-phosphate
  • Ascorbic Acid
  • Oxygen