2006 Fiscal Year Final Research Report Summary
Analysis of radiation induced genomic instability via reversion from the tandem duplication of specific gene as a marker of mutation.
| Project/Area Number |
17510060
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Risk sciences of radiation/Chemicals
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| Research Institution | Radiation Effects Research Foundation |
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Principal Investigator |
NODA Asao Radiation Effects Research Foundation, Department of Genetics, Chief of Cytogenetics Lab., 遺伝学部・細胞遺伝学室長 (40294227)
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| Co-Investigator(Kenkyū-buntansha) |
KODAMA Yoshiaki Radiation Effects Research Foundation, Department of Genetics, Assistant Chief, 遺伝学部, 副部長 (60359453)
NAKAMURA Nori Radiation Effects Research Foundation, Chief Scientist, 主席研究員 (00010116)
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| Project Period (FY) |
2005 – 2006
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| Keywords | genomic instability / radiation / HPRT |
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| Research Abstract |
Tandem repeat sequences, classified as minisatellite sequences or partially duplicated genes, are inherently unstable. Radiation exposure can increase such repeat sequence instability, but the biological consequences of this elevated instability are not well characterized. To learn more about the characteristics of the instability at different sequences in the genome, we created mutant HT1080 cells bearing a 8.4 kb of partially duplicated allele at the HPRT locus by gene targeting. The cells were then tested to determine whether or not repeat-sequence instability (assessed by elevated reversion rate caused by loss of one duplicated segment) accompanied increased forward mutation rates at the restored wild-type HPRT allele. Following a 4 Gy X-irradiation, 26 clones were selected (out of 500 clones, 6%) which showed elevated reversion rates even after many cell generations. These clones also showed general increase in the forward mutation rate, whereas the paired individual mutation rates did not correlate with each other. Furthermore, levels of intracellular reactive oxygen species (ROS) and nuclear yH2AX foci, which is a hallmark for DNA damage responses, were also generally elevated although they did not correlate with the individual reversion rates. It was concluded that repeat sequence instability is not predictive of unique sequence instability, probably because the instability is generated by multiple mechanisms following radiation exposure.
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