2004 Fiscal Year Final Research Report Summary
Analyses for Genes Controlling Susceptibility to Radiation-Induced Tumorigenesis
| Project/Area Number |
14580571
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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 |
環境影響評価(含放射線生物学)
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| Research Institution | Osaka Prefecture University |
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Principal Investigator |
MORI Nobuko Osaka Prefecture University, Res.Inst.Advan.Sci. & Technol., Assistant Professor, 先端科学研究所, 講師 (90100221)
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| Co-Investigator(Kenkyū-buntansha) |
OKUMOTO Masaaki Osaka Prefecture University, Res.Inst.Advan.Sci. & Technol., Professor, 先端科学研究所, 教授 (50100186)
YAMATE Jyoji Osaka Prefecture University, Grad.Sc.Agri.Biol.Sci., Associate Professor, 大学院・農学生命科学研究科, 助教授 (50150115)
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| Project Period (FY) |
2002 – 2004
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| Keywords | lymphoma / radiation carcinogenesis / tumor susceptibility / mouse / genetic analysis |
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| Research Abstract |
(1)Genome-wide screening for tumor susceptibility in [(BALB/c x STS)F1 x STS] mice subjected to 4 x 1.7 Gy X-irradiation detected no chromosomal segment carrying homozygous STS allele, which could achieve tumor resistance equivalent to that of STS mice. This indicates that resistance to lymphomagenesis in STS mice is not under a single gene control. Suggestive (not significant) linkage was detected in the segment close to Pten on chromosome 19 and at a marker D1Mit14 near the telomere of chromosome 1.
(2)Linkage analysis using [(BALB/c x STS)F1 x BALE/c] mice identified two loci responsible for tumor susceptibility on chromosome 4, where the STS allele conferred resistance to lymphomagenesis (chi square values were more than 15.3). One locus located in the vicinity of D4Mit17 (30 cM distal to the centromere) and nearby D4Mit9, INK4a and b, approximately 10 cM distal to the locus, another locus existed. Analysis of several congenic lines bearing various portions of STS-derived chromosome 4 in the BALB/c background confirmed the presence of a tumor susceptibility gene in a 10 Mb region containing these INK4 family genes. Experiments to confirm the existence of another susceptibility gene for lymphomagenesis are ongoing by using a set of congenic mouse lines.
(3)A single exposure to 4 Gy of X-irradiation induced mammary tumors with a frequency less than that of lymphomas in p53 hemizygous mice with the BALE/c background. Furthermore, in the p53 hemizygous mice 4 times irradiation with an X-ray dose less than 1 Gy at a week interval doubled the mammary tumor frequency in compensation for a reduced incidence of lymphomas. Using a genetic cross between (C57BL/6 x p53 hemizygous BALB/c)F1 and BALB/c linkage analysis for mammary tumor susceptibility is presently under way.
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