Replication of murine mitochondrial DNA following irradiation.
The effect of radiation on the mitochondrial genome in vivo is largely unknown. Though mitochondrial DNA (mtDNA) is vital for cellular survival and proliferation, it has little DNA repair machinery compared with nuclear DNA (nDNA). A better understanding of how radiation affects mtDNA should lead to new approaches for radiation protection. We have developed a new system using real-time PCR that sensitively detects the change in copy number of mtDNA compared with nDNA. In each sample, the DNA sequence coding 18S rRNA served as the nDNA reference in a run simultaneously with a mtDNA sequence. Small bowel collected 24 hours after 2 Gy or 4 Gy total body irradiation (TBI) exhibited increased levels of mtDNA compared with control mice. A 4 Gy dose produced a greater effect than 2 Gy. Similarly, in bone marrow collected 24 hours after 4 Gy or 7 Gy TBI, 7 Gy produced a greater response than 4 Gy. As a function of time, a greater effect was seen at 48 hours compared with 24 hours. In conclusion, we found that radiation increased the ratio of mtDNA:nDNA and that this effect seems to be tissue independent and seems to increase with radiation dose and duration following radiation exposure.
Zhang
Hengshan
H
Department of Radiation Oncology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Maguire
David
D
Swarts
Steven
S
Sun
Weimin
W
Yang
Shanmin
S
Wang
Wei
W
Liu
Chaomei
C
Zhang
Mei
M
Zhang
Di
D
Zhang
Louie
L
Zhang
Kunzhong
K
Keng
Peter
P
Zhang
Lurong
L
Okunieff
Paul
P
D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics*; D018628:Gene Dosage / Q000235:genetics; D007421:Intestine, Small / Q000378:metabolism* / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000187:drug effects*; D016133:Polymerase Chain Reaction; D013997:Time Factors
D004272:DNA, Mitochondrial