2007 Fiscal Year Final Research Report Summary
Infulence of p53 on the induction of mouse skin tumors by repetitive beta-irradiation
| Project/Area Number |
16310046
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
OOTSUYAMA Akira University of Occupational and Environmental Health, Japan, School of Med., Assoc. Prof. (10194218)
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| Co-Investigator(Kenkyū-buntansha) |
NORIMURA Toshiyuki University of Occupational&Environmental Health, Japan, School of Med., Prof. (20039530)
KATO Fumio University of Occupational&Environmental Health, Japan, School of Med., Res. Assoc. (20309959)
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| Project Period (FY) |
2004 – 2007
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| Keywords | P53 gene / KO mouse / Beta-irradiation / repetitive irradiation / skin cancer / radiation carcinogenesis |
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| Research Abstract |
Introduction: We studied about a protection mechanism of p53 gene against a radiation induced teratogenesis using p53 (-/-) mice (KO), a p53 (+/-) mice (hetero) and a p53 (+/+) mice (wild). In wild mice, p53 dependent and independent DNA repair mechanisms restore DNA damages together, and then unrestorable damage cells are removed by p53 dependent apoptosis effectively after low dose rate radiation (LDR). Therefore the teratogenic rate keeps control level. On the other hand, in a KO mice, p53 independent DNA repair mechanism works, but p53 dependent DNA repair mechanism and apoptosis don' t work. So the teratogenic rate does not decrease to a control level at even low dose rate irradiation in KO mice. (Kato F, et. al. Int. J. Radiat. Biol. 77, 13-, 2001) In the DNA damage after LDR, it is thought there are similar mechanisms in processes of carcinogenesis and teratogenesis. In this study, with the mice same as an above it, we investigate whether a p53 gene has mechanisms to remove dama
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ges by not only DNA repair mechanism but also apoptosis on radiation carcinogenesis process. In wild mice, if a repair of DNA damages and removing of damage cells by apoptosis are almost completely performed on repetitive LDR, the cancer might not occur. But under the same experimental condition, if the cancer occurs in KO mice, it is thought there is a threshold dose on radiation carcinogenesis process.
Method: Seven weeks old mice were used. The backs of the mice were irradiated with beta-rays three times a week until occurrence of tumor or throughout the life of the mice. Beta-rays source: <90>Sr^-^<90>Y disk, 1.85GBq, 15Gy/min. Group I: 2.SGy/day. Group II: 5Gy/day. P53 genes extracted from the tumors were analyzed about LOH and mutation.
Results: In KO mice, we did not found occurrence of tumor. In hetero mice, we found 8/21 and 25/45 of tumor incidence in Group I and Group II. In wild mice, we found 2/8 and 6/33 of tumor incidence in Group I and Group II, and appearance time of the tumors was about 150days later than that of hetero mice. In hetero mice, 17/26 of tumors had LOH of p53 but had not mutations. In wild mice, 7/9 of tumors had mutations and 1/7 of tumor had LOH.
Conclusion: An existence state of a p53 gene affects the tumor-causing time and incidence obviously. Types of variation of a p53 gene may be different by an existence state of a p53 gene Less
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Research Products
(9 results)
