1993 Fiscal Year Final Research Report Summary
Studies on expression of radiation damage and modifying repair mechanisms
| Project/Area Number |
04304056
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| Research Category |
Grant-in-Aid for Co-operative Research (A)
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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 | National Institute of Radiological Sciences |
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Principal Investigator |
SATO Kouki Nat.Inst.Radiol.Sci., Div.Radiat.Hazards Director, 障害基礎研究部, 部長 (60029775)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAGI N. Hokkaido Univ., Grad.Sch.Environ.Earth Sci.Professor, 地球環境科学研究科, 教授 (20001852)
SHIMA A. Univ.Tokyo, Facul.Sci.Professor, 理学部, 教授 (60011590)
SENO T. Nat.Inst.Genetics, Dept.Mol.Genetics Professor, 変異遺伝研究部門, 教授 (30076989)
NIKAIDO O. Kanazawa Univ., Facul.Pharmaceu.Sci.Professor, 薬学部, 教授 (60019669)
YASUI A. Inst.Develop.Aging Cancer, Dept.Neurochem.Mol.Biol.Professor, 神経機能情報研究分野, 教授 (60191110)
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| Project Period (FY) |
1992 – 1993
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| Keywords | DNA strand break / photolyase / excision repair / UV skin cancer / germ cell mutation / X chromosome inactivation / threshold-like response / restriction length polymorphism |
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| Research Abstract |
We have demonstrated that the two mammalian cell mutants are hyper-sensitive to ionizing radiation and deficient in the repair of DNA double-strand breaks and that one of the repair genes is located on human chromosome 5. The photolyase genes from blue-green algae, insects, fish and rat kangaroo have been cloned and their base sequences have been determined. The human gene ERCC5 which normalizes the defect in an excision repair-deficient mutant has been cloned and sequenced, which is identical to the gene of human xeroderma pigmentosum group G.A skin carcinogenesis system has been established using experimental animals and the use of damage-specific monoclonal antibodies has revealed that the solar light-induced lesions in the skin increase with dose and disappear within 24 hours. A murine temperature-sensitive mutant of ubiquitin-activating enzyme is arrested at the G2 phase at restrictive temperature and undergoes pulverization of the chromosomes. Spontaneous germ cell mutation frequency in medaka (Oryzias latipes) is similar to that in mouse and dadiation-induced mutation frequency differs substantially according to the stages of differentiation and mutation. Mouse embryos that have the sex chromosome composition of XXY develop normally when an excess X is paternal but develop aberrantly when an excess X is maternal. The reason for this phenomenon is that maternal X chromosomes are inactivated. Repeated beta-ray irradiation (3 times a week) of mouse skin causes cancer in all animals but the one-time dose of 0.5 Gy causes no cancer during their lifetime. Hence the radiation carcinogenesis of mouse skin shows a threshold-like response. Most of the radiation-induced thymiclymphoma are derived from single cells and they are accompanied by clone-specific chromosomal aberrations. Female patients with hematopoietic diseases have been diagnosed using restriction fragment length polymorphism.
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