Inhibition of mitochondrial function reduces DNA repair in human mononuclear cells

Leuk Res. 2011 Feb;35(2):219-25. doi: 10.1016/j.leukres.2010.06.009. Epub 2010 Jul 8.

Abstract

Background: Mitochondria provide ATP and Ca(2+) needed for DNA repair, but also produce reactive oxygen species (ROS), which may damage DNA.

Aim: To investigate the effect of mitochondrial function inhibition on DNA repair.

Method: Five mitochondrial inhibitors acting at various sites of electron transport were studied. Human peripheral blood mononuclear cells, spontaneous and H(2)O(2)-induced DNA repair, as well as %-double-stranded-DNA, were measured.

Results: All mitochondrial inhibitors suppressed spontaneous and H(2)O(2)-induced DNA repair. However, their effect on %-double-stranded-DNA differed, which is partly related to ROS suppression.

Conclusion: Mitochondrial inhibition may enhance efficacy and reduce toxicity of radiation and cytotoxic drugs therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Repair / drug effects
  • DNA Repair / physiology*
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism*
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Reactive Oxygen Species / metabolism
  • Uncoupling Agents / pharmacology

Substances

  • Reactive Oxygen Species
  • Uncoupling Agents