| Project/Area Number |
04680211
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
放射線5生物学
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
YAGI Takashi Kyoto University, Faculty of Medicine, Associate Prof., 医学部, 助教授 (80182301)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1993: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1992: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | DNA repair / Mutation / radiation / Ultraviolet / Xeroderma pigmentosum / Tumor suppressor gene / 高発がん性遺伝病 |
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| Research Abstract |
The frequency and type of radiation-induced mutations were compared among the cells having different DNA repair mechanisms and between in vitro and in vivo. UV mainly induced G : C to A : T transition mutation in all cells, and the mutation was higher in DNA repair-deficient xeroderma pigmentosum (XP) cells than in normal human and mouse cells. This shows that normal human and mouse cells sustained the similar type of mutation by UV regardless of their different DNA repair mechanism.
The PCR-SSCP analysis revealed that about half of skin tumors developed in sun-exposed area of XP patients have mutations in p53 gene. The most frequent type of mutation was the C to T transition at 5'-TC and 5'-CC dipyrimidine sequences, which were similar to the type of UV-induced mutation in vitro. No mutation was detected in skin tumors from the XP patients. These results indicate that the mutations in p53 gene were induced by sunlight UV, and not ras genes but the p53 gene plays an important role in skin tumor development.
Transfection of the normal Ha-ras sequence irradiated with UV produced transformed-foci in mouse BALB3T3 cells. The ras sequences retrieved from the transformed-foci have point mutations. The most frequent type of mutation was the C to T transition at 5'-TC or 5'-CC in codons 12, 13 and 60 in the ras sequence. These results indicate that UV induces mutations which confer transforming activity to ras genes but the ras gene mutations do not lead to tumor development in the skin of XP patients.
This study showed that the different type of mutation were induced by UV between the cells with different DNA repair ability, and the type of mutations found in p53 gene in skin tumors in XP patients is reflected to the type of UV-induced mutation.
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