Inhibition of mitochondrial function reduces DNA repair in human mononuclear cells.
BACKGROUND
Mitochondria provide ATP and Ca(2+) needed for DNA repair, but also produce reactive oxygen species (ROS), which may damage DNA.


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


METHODS
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.


CONCLUSIONS
Mitochondrial inhibition may enhance efficacy and reduce toxicity of radiation and cytotoxic drugs therapy.
Gafter-Gvili
Anat
A
Department of Hematology, Rabin Medical Center, Petah Tikva, Israel.
Herman
Michal
M
Ori
Yaacov
Y
Korzets
Asher
A
Chagnac
Avry
A
Zingerman
Boris
B
Rozen-Zvi
Benaya
B
Gafter
Uzi
U
Malachi
Tsipora
T
D004260:DNA Repair / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014475:Uncoupling Agents / Q000494:pharmacology
D017382:Reactive Oxygen Species; D014475:Uncoupling Agents