1992 Fiscal Year Annual Research Report

放射線被曝による継世代発がん

Research Project

Project/Area Number	04151038
Research Institution	Osaka University
Principal Investigator	野村大成大阪大学, 医学部, 教授 (90089871)
Co-Investigator(Kenkyū-buntansha)	加藤秀樹実験動物中央研究所, 室長 (30142053) 渡辺敦光広島大学, 原爆放射能医学研究所, 助教授 (00034653) 佐々木正夫京都大学, 放射線生物研究センター, 教授 (20013857) 馬淵清彦放射線影響研究所, 部長藤堂剛大阪大学, 医学部, 助手 (90163948)
Keywords	継世代発がん / 放射線被曝 / ヒト / マウス
Research Abstract	「放射線被曝による継世代発がん」に関して、ヒトにおいては、馬淵班員が広島・長崎の被爆者のF_1集団72,000人の調査を行った。1946-89年の死亡者中で白血病63症例、リンパ腫22症例を発見したので、詳しい診断を確認の上、授精前被曝との相関が調査できるようになった。基礎研究では、渡辺班員がC3H雄マウスに^<252>Cf中性子放射線照射することにより、ヘパトーマが非照射F_1(3%)の14倍の頻度で発生していることを発見し、野村実験を異なった系統マウスと原爆類似放射能で確認した。野村は、LTマウスにX線(3.6Gy)を照射することによりF_1に10倍の頻度で白血病が誘発されることを発見した。ICRマウスでは見られなかったことである。加藤班員は、これらF_1での発がんに関与した遺伝子のマッピングのため、TemplateDNAの多量、短時間処理法を確立した。佐々木班員はヒトにおける父親由来の突然変異としてRb遺伝子を調べ、Rb腫瘍細胞では80%の症例に+1g異常が観察されるが、9例中8例までが母親由来の1gが過剰になっていることが分かった。新しい発見であり、今後大きな問題になるだろう。藤堂班員は、紫外線によるDNA損傷のうち、がんや突然変異と深く関与してると思われる6-4産物を特異的に修復する酸素を初めて発見した。国内外で大きな反響を呼び、新聞誌上でも大きく報道された。英国核施設従業員(父親)の授精前被曝によりF_1にリンパ性白血病が相対リスク9.0(P=0.047)の高さで発生しているとの報告が1993年3月6日にあった(BMJ)。この報告は、Gardner論文と同じく野村のマウス実験と一致しており、より一層、ヒト疫学、マウスを用いた基礎研究が必要となる。また、内部被曝や低線量率長期被曝の精原細胞および卵細胞におよぼす影響がクローズアップされるようなった。

Research Products

(22 results)

All Other

All Publications (22 results)

[Publications] Nomura,T.: "Programmed cell death in whole body and organ system by low dose rediation." Journal of Radiation Research. 33. 109-123 (1992)
[Publications] Ohmori,H.: "Comparison of ki-ras gene mutation among simultanconely occurring multiple urethane-induced lung tumors in individual mice." Carcinogenesis. 13. 851-855 (1992)
[Publications] Sasai,H.: "Syrian hamster embryo cell lines useful for detecting transforming genes in mouse tumours:detection of transforming genes in X-ray-related mouse tumours." British Journal of Cancer. 67. 262-267 (1993)
[Publications] Todo,T.: "A new photoreactivating cnzyme that specifically repairs ultraviolet light-induced (6-4) phtoproducts." Nature. 361. 371-374 (1993)
[Publications] Mabuchi,K.: "Future epidemiologic studies of lung cancer in A-bomb survivors." BIR Report. 21-25 (1992)
[Publications] Neel,J.V.: "¨Rogue¨lymphocytes among Ukrainians not exposed to radioactive fall-out from the chernobyl accident:The possible role of this phenomenon in oncogenesis,teratogenesis,and mutagenesis." Proc.Natl.Acad.sci.89. 6973-6977 (1992)
[Publications] Sposto,R.: "The effect of diagnostic misclassification on non-canser and cancer mortality dose response in A-bomb surviviors." Biometrics. 48. 605-617 (1992)
[Publications] Watanabe,H.: "The effects of sodium chloride,miso,or ethanol on intestinal,metaplasia induced by X-irradiationin rats." Japanese Journal of Cancer Research. 83. 1267-1272 (1992)
[Publications] Ito,A.: "Significance of strain and sex differences in the development of ^<252>Cf neutron-induced liver tumors in mice." Japanese Journal of Cancer Research. 83. 1052-1056 (1992)
[Publications] Takahashi,T.: "^<252>Cf relative biological effectiveness and inheritable effects of fission neutrons in mouse liver tumorigenesis." Cancer Research. 52. 1948-1953 (1992)
[Publications] Wu,X.: "Genetic profile of LIBP/1 inbred strain derived from the kunming outbred stock of the mouse." Exp.Anim.41. 541-543 (1992)
[Publications] Kubota,K.: "Correlation of myc expression with the growth-arrested and transformed phenotypes in hybrids between a T lymphoma and an antigen-responsive T-cell line." International Journal of Cancer. 51. 927-934 (1992)
[Publications] Sasaki,M.S.: "Some considerations on the modulation of radiation-induced genetic damage by cellular stress vesponse." Yokohama Med.Bull.42. 18-22 (1992)
[Publications] Sasaki,M.S.: "Cytogenetic biomonitoring of human radiation exposures:possibillties,problems and pitfalls." Journal of Radiation Research. 33. 44-53 (1992)
[Publications] Yamaguchi,T.: "Allelotype analysis in osteosarcomas:frequent allele loss on 3q,13q,17p,and 18q." Cancer Research. 52. 2419-2423 (1992)
[Publications] Toguchida,J.: "Prevalence and spectrum of germinal mutations of the p53 gene among patients with sarcoma." New Engl.J.Med.326. 1301-1304 (1992)
[Publications] Tanaka,K.: "Hepatoblastoma in a 2-year-old girl with trisomy 18." Eur.J.Pediatr.Surg.2. 298-300 (1992)
[Publications] Kyoizumi,S.: "Frequency of mutant T lymphocytes defective in the expression of the T-cell antigen receptor gene among radiation-exposed people." Mutation Research. 265. 173-180 (1992)
[Publications] Nomura,T.: "Low Dose Irradiation and Biological Defense Mechanism" Elsevier, 150 (1992)
[Publications] Nomura,T.: "Low Dose Radiation and Living State" Narosa Publication, (1993)
[Publications] Nomura,T.: "Male-mediated Developmental Toxicity" Plenum Press, (1993)
[Publications] Katoh,H.: "Molocular Approaches to the Study and Treatment of Human Diseases" Elsevier, 6 (1992)

1992 Fiscal Year Annual Research Report

放射線被曝による継世代発がん

Principal Investigator

野村 大成 大阪大学, 医学部, 教授 (90089871)

Research Products

[Publications] Nomura,T.: "Programmed cell death in whole body and organ system by low dose rediation." Journal of Radiation Research. 33. 109-123 (1992)

[Publications] Ohmori,H.: "Comparison of ki-ras gene mutation among simultanconely occurring multiple urethane-induced lung tumors in individual mice." Carcinogenesis. 13. 851-855 (1992)

[Publications] Sasai,H.: "Syrian hamster embryo cell lines useful for detecting transforming genes in mouse tumours:detection of transforming genes in X-ray-related mouse tumours." British Journal of Cancer. 67. 262-267 (1993)

[Publications] Todo,T.: "A new photoreactivating cnzyme that specifically repairs ultraviolet light-induced (6-4) phtoproducts." Nature. 361. 371-374 (1993)

[Publications] Mabuchi,K.: "Future epidemiologic studies of lung cancer in A-bomb survivors." BIR Report. 21-25 (1992)

[Publications] Neel,J.V.: "¨Rogue¨lymphocytes among Ukrainians not exposed to radioactive fall-out from the chernobyl accident:The possible role of this phenomenon in oncogenesis,teratogenesis,and mutagenesis." Proc.Natl.Acad.sci.89. 6973-6977 (1992)

[Publications] Sposto,R.: "The effect of diagnostic misclassification on non-canser and cancer mortality dose response in A-bomb surviviors." Biometrics. 48. 605-617 (1992)

[Publications] Watanabe,H.: "The effects of sodium chloride,miso,or ethanol on intestinal,metaplasia induced by X-irradiationin rats." Japanese Journal of Cancer Research. 83. 1267-1272 (1992)

[Publications] Ito,A.: "Significance of strain and sex differences in the development of ^<252>Cf neutron-induced liver tumors in mice." Japanese Journal of Cancer Research. 83. 1052-1056 (1992)

[Publications] Takahashi,T.: "^<252>Cf relative biological effectiveness and inheritable effects of fission neutrons in mouse liver tumorigenesis." Cancer Research. 52. 1948-1953 (1992)

[Publications] Wu,X.: "Genetic profile of LIBP/1 inbred strain derived from the kunming outbred stock of the mouse." Exp.Anim.41. 541-543 (1992)

[Publications] Kubota,K.: "Correlation of myc expression with the growth-arrested and transformed phenotypes in hybrids between a T lymphoma and an antigen-responsive T-cell line." International Journal of Cancer. 51. 927-934 (1992)

[Publications] Sasaki,M.S.: "Some considerations on the modulation of radiation-induced genetic damage by cellular stress vesponse." Yokohama Med.Bull.42. 18-22 (1992)

[Publications] Sasaki,M.S.: "Cytogenetic biomonitoring of human radiation exposures:possibillties,problems and pitfalls." Journal of Radiation Research. 33. 44-53 (1992)

[Publications] Yamaguchi,T.: "Allelotype analysis in osteosarcomas:frequent allele loss on 3q,13q,17p,and 18q." Cancer Research. 52. 2419-2423 (1992)

[Publications] Toguchida,J.: "Prevalence and spectrum of germinal mutations of the p53 gene among patients with sarcoma." New Engl.J.Med.326. 1301-1304 (1992)

[Publications] Tanaka,K.: "Hepatoblastoma in a 2-year-old girl with trisomy 18." Eur.J.Pediatr.Surg.2. 298-300 (1992)

[Publications] Kyoizumi,S.: "Frequency of mutant T lymphocytes defective in the expression of the T-cell antigen receptor gene among radiation-exposed people." Mutation Research. 265. 173-180 (1992)

[Publications] Nomura,T.: "Low Dose Irradiation and Biological Defense Mechanism" Elsevier, 150 (1992)

[Publications] Nomura,T.: "Low Dose Radiation and Living State" Narosa Publication, (1993)

[Publications] Nomura,T.: "Male-mediated Developmental Toxicity" Plenum Press, (1993)

[Publications] Katoh,H.: "Molocular Approaches to the Study and Treatment of Human Diseases" Elsevier, 6 (1992)

野村大成大阪大学, 医学部, 教授 (90089871)