TY - JOUR
T1 - Analysis of Common Deletion (CD) and a novel deletion of mitochondrial DNA induced by ionizing radiation
AU - Wang, Lu
AU - Kuwahara, Yoshikazu
AU - Li, Li
AU - Baba, Taisuke
AU - Shin, Ryong Woon
AU - Ohkubo, Yasuhito
AU - Ono, Koji
AU - Fukumoto, Manabu
N1 - Funding Information:
This study was supported in part by Grants-in-Aid from the Ministry of Education, Science, Sports and Culture and the Ministry of Health, Labor and Welfare of Japan and in collaboration with Center for Interdisciplinary Research, Tohoku University.
PY - 2007
Y1 - 2007
N2 - Purpose: In order to identify supportive evidence of radiation exposure to cells, we analyzed the relationship between exposure to ionizing radiation and the induction of deletions in mitochondrial DNA (mtDNA). Materials and methods: Using human hepatoblastoma cell line, HepG2 and its derivatives, HepG2-A, -89 and -400, established after long term exposure to X-ray, mtDNA deletions were analyzed by polymerase chain reaction (PCR) and real-time PCR after cells were subjected to radiation and genotoxic treatments. Results: Common Deletion (CD), the most extensively studied deletion of mtDNA, was induced within 24 h after exposure to 5 Gray (Gy) of X-rays and was associated with replication of mtDNA. CD became undetectable several days after the exposure due to the death of cells containing mitochondria within which CD had been induced. Furthermore, we found a novel mtDNA deletion that consisted of a 4934 base-pair deletion (4934del) between nucleotide position 8435 and 13,368. A lower dose of ionizing radiation was required to induce the 4934del than for CD and this was independent of the quality of radiation used and was not induced by treatments with hydrogen peroxide (H2O2) and other genotoxic reagents including bleomycin. Conclusion: CD is induced by ionizing radiation, however, the amount of CD detected at a certain point in time after radiation exposure is dependent on the initial frequency of CD induced and the death rate of cells with mtDNA containing CD. The novel mtDNA deletion found in this study, therefore, will be used to determine whether cells were exposed to ionizing radiation.
AB - Purpose: In order to identify supportive evidence of radiation exposure to cells, we analyzed the relationship between exposure to ionizing radiation and the induction of deletions in mitochondrial DNA (mtDNA). Materials and methods: Using human hepatoblastoma cell line, HepG2 and its derivatives, HepG2-A, -89 and -400, established after long term exposure to X-ray, mtDNA deletions were analyzed by polymerase chain reaction (PCR) and real-time PCR after cells were subjected to radiation and genotoxic treatments. Results: Common Deletion (CD), the most extensively studied deletion of mtDNA, was induced within 24 h after exposure to 5 Gray (Gy) of X-rays and was associated with replication of mtDNA. CD became undetectable several days after the exposure due to the death of cells containing mitochondria within which CD had been induced. Furthermore, we found a novel mtDNA deletion that consisted of a 4934 base-pair deletion (4934del) between nucleotide position 8435 and 13,368. A lower dose of ionizing radiation was required to induce the 4934del than for CD and this was independent of the quality of radiation used and was not induced by treatments with hydrogen peroxide (H2O2) and other genotoxic reagents including bleomycin. Conclusion: CD is induced by ionizing radiation, however, the amount of CD detected at a certain point in time after radiation exposure is dependent on the initial frequency of CD induced and the death rate of cells with mtDNA containing CD. The novel mtDNA deletion found in this study, therefore, will be used to determine whether cells were exposed to ionizing radiation.
KW - Cell death
KW - Deletion
KW - Ionizing radiation
KW - Mitochondrial DNA
UR - http://www.scopus.com/inward/record.url?scp=34249774584&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34249774584&partnerID=8YFLogxK
U2 - 10.1080/09553000701370878
DO - 10.1080/09553000701370878
M3 - Article
C2 - 17538793
AN - SCOPUS:34249774584
VL - 83
SP - 433
EP - 442
JO - International Journal of Radiation Biology
JF - International Journal of Radiation Biology
SN - 0955-3002
IS - 7
ER -