Altered mitochondrial function and genome frequency post exposure to &#x03B3;-radiation and bystander factors.
OBJECTIVE
To further evaluate irregular mitochondrial function and mitochondrial genome damage induced by direct γ-irradiation and bystander factors in human keratinocyte (HPV-G) epithelial cells and hamster ovarian fibroblast (CHO-K1) cells. This is as a follow-up to our recent reports of γ-irradiation-induced loss of mitochondrial function and mitochondrial DNA (mtDNA) damage.


METHODS
Mitochondrial function was evaluated post direct radiation and irradiated cell conditioned medium (ICCM) by determining: Activity of the individual complexes of oxidative phosphorylation (OxPhos); mtDNA-encoded protein synthesis; and mitochondrial genome frequency and mtDNA damage.


RESULTS
Mitochondria show a loss of OxPhos enzyme function as early as 4 h post treatment with recovery observed 12-96 h in some but not all complexes demonstrating a non-uniform sensitivity to γ-radiation. We also identified irregular mtDNA-directed protein synthesis. Long range Polymerase Chain Reaction (PCR) analysis identified mitochondrial genome damage and real-time PCR identified increases in mitochondrial genome frequency.


CONCLUSIONS
The study reaffirms the sensitive nature of mitochondria to both low-level direct radiation exposure and radiation-induced bystander factor mediated damage. Furthermore, we report for the first time, the loss of function in the enzymes of OxPhos post exposure to bystander factors and identify altered mtDNA-directed protein synthesis post both direct radiation and bystander factors.
Nugent
Sharon
S
Radiation and Environmental Science Centre, Focas Institute, Dublin Institute of Technology, Ireland.
Mothersill
Carmel E
CE
Seymour
Colin
C
McClean
Brendan
B
Lyng
Fiona M
FM
Murphy
James E J
JE
D000818:Animals; D024201:Bystander Effect / Q000235:genetics / Q000528:radiation effects*; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004272:DNA, Mitochondrial / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D005720:Gamma Rays; D016678:Genome / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects*; D010085:Oxidative Phosphorylation / Q000528:radiation effects; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis / Q000528:radiation effects
D004272:DNA, Mitochondrial