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Inhibition of mitochondrial function reduces DNA repair in human mononuclear cells
Authors:Anat Gafter-Gvili  Michal Herman  Yaacov Ori  Asher Korzets  Avry Chagnac  Boris Zingerman  Benaya Rozen-Zvi  Uzi Gafter  Tsipora Malachi
Affiliation:a Department of Nephrology and Hypertension, Rabin Medical Center, Petah Tikva, Israel
b Department of Hematology, Rabin Medical Center, Petah Tikva, Israel
c Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Abstract:

Background

Mitochondria provide ATP and Ca2+ 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 H2O2-indcued DNA repair, as well as %-double-stranded-DNA, were measured.

Results

All mitochondrial inhibitors suppressed spontaneous and H2O2-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.
Keywords:DNA breaks   Spontaneous DNA repair   H2O2-indcued DNA repair   %-Double-stranded-DNA   Mitochondrial inhibitors   Human peripheral blood mononuclear cells   3H-thymidine incorporation
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