| Project/Area Number |
63480506
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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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 | Osaka University |
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Principal Investigator |
NOMURA Taisei Osaka Univ., Fac. Med., Professor, 医学部 教授 (90089871)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Osamu Hiroshima Univ., Fac. Sci., Professor, 理学部, 教授 (80034627)
ISHII Yutaka Osaka Univ., Fac. Med., Assoc. Professor, 医学部, 助教授 (20028509)
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| Project Period (FY) |
1988 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 1990: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1989: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1988: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Radiation / Chemicals / Transgeneration effects / Malformations / Functional defects / Mouse / Mutation / Genetic risk / ENU / 仮死 / ウレタン / DMBA |
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| Research Abstract |
Radiation and chemicals are well known to produce visible and lethal mutations in higher plants and animal. Especially, extensive works have been done by specific loci method, etc. In mice, but large numbers of animals are necessary to test a variety of chemicals by these established methods. Recently, Nomura found that parental exposure to radiation can cause congenital malformations in the next generation in mice. Furthermore, induced malformations in F_1 offspring were similar to those found in humans. Experimental results obtained in the term of this project were summa-rized as follows.
(1) Establishment of a method to detect germ-line mutation causing congenital malformation and its application to chemicals : Preconceptional treatment with ENU, DMBA and 4NQO as well as X-rays induced a significant incidence of congenital malformations in the F_1 offspring. In contrast to X-rays, spermatogonial stage was more sensitive to ENU than post-meiotic stages as it was in the specific locus mutation.
(2) Detection of functional defects by germinal mutation : Parental exposure to ENU and X-rays caused a significant incidence of respiratory distress in F_1 fetuses, and a half of them were not accompanied with morphological malformations.
(3) Heritability of induced malformations in the offspring : Dwarfism and tail anomalies inherited as a dominant trait with reduced expressivity.
(4) Damage to fertilization capacity of the sperm : Very low doses of AS and LAS interrupted fertilization capacity of the human and mouse sperm to golden hamster eggs.
(5) WHO recommendation : Germ-line alterations causing congenital malformation in F_1 offspring was adopted as a method to detect genetic hazards.
(6) Future problems : Clinical and epidemiological survey should be performed. Functional defects will become more important in human population.
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