TY - JOUR
T1 - Inhibition of mitochondrial function reduces DNA repair in human mononuclear cells
AU - Gafter-Gvili, Anat
AU - Herman, Michal
AU - Ori, Yaacov
AU - Korzets, Asher
AU - Chagnac, Avry
AU - Zingerman, Boris
AU - Rozen-Zvi, Benaya
AU - Gafter, Uzi
AU - Malachi, Tsipora
N1 - Funding Information:
This study was supported by a grant from Teva Medical Ltd., Netanya, Israel.
PY - 2011/2
Y1 - 2011/2
N2 - 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.
AB - 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.
KW - %-Double-stranded-DNA
KW - 3H-thymidine incorporation
KW - DNA breaks
KW - HO-indcued DNA repair
KW - Human peripheral blood mononuclear cells
KW - Mitochondrial inhibitors
KW - Spontaneous DNA repair
UR - http://www.scopus.com/inward/record.url?scp=78751705531&partnerID=8YFLogxK
U2 - 10.1016/j.leukres.2010.06.009
DO - 10.1016/j.leukres.2010.06.009
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C2 - 20619454
AN - SCOPUS:78751705531
SN - 0145-2126
VL - 35
SP - 219
EP - 225
JO - Leukemia Research
JF - Leukemia Research
IS - 2
ER -