1994 Fiscal Year Annual Research Report

放射線被爆による継世代発がん

Research Project

Project/Area Number	06280111
Research Institution	Osaka University
Principal Investigator	藤堂剛大阪大学, 医学部 (90163948)
Co-Investigator(Kenkyū-buntansha)	加藤秀樹実験動物中央研究所, 遺伝研究室, 室長(研究員) (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, 疫学部, 部長(研究員) 野村大成大阪大学, 医学部, 教授 (90089871)
Keywords	継世代発がん / 放射線被爆 / ヒト / マウス / 父親起源突然変異 / P53 / Rb
Research Abstract	1.マウスを用いた継世代発がん:野村はLTマウスを用い精子および精子細胞期へのX線(5.04Gy)照射により、F_1マウス非照射群の約10倍の頻度でリンパ性白血病が誘発されたが、精原細胞期照射ではICRマウスと同様に白血病は誘発されなかった。本年度は、N5マウスを用いたところ、精原細胞期照射でも約6倍の頻度でリンパ性白血病が発生し、ICR,LTと異なる結果となった。白血病発生に系統差がある。また、渡辺は原爆放射能に近い線室の^<252>Cf(中性子66%)をC3H雄マウスの精子期あるいは精原細胞期に1回全身照射(O.5,1.0Gy)し、C57BL雌マウスと交配し、F_1を14.5ケ月後に屠殺したところ、いずれの群でも、肝腫瘍が約10倍も増加した。 2.原爆被爆者の子供の死亡率調査:両親の被爆線量に伴う、全死因及び癌死亡の有意な増加は認められない。発癌率調査でも殆ど認められないであろう(馬淵)。 3.継世代発がん機序:マウスにおける継世代発がんの遺伝様式はヒトでのRB遺伝子やp53遺伝子の変異によるがん発生と似ている。 1)網膜芽細胞腫患者の突然変異の起源を調べると情報の得られた16例のうち15例までが父親由来であり、微視突然変異(RB1)では67%に欠失・挿入・塩基置換なとどの突然変異が認められた(佐々木)。 2)継世代高発がんN5マウス家系においてもp53の変異が検出された(野村)。 3)マウス肺腫瘍の発生には、その70%を決定する単一の優性遺伝子が存在し、マイクロサテライトマーカーを用い調べると、第六染色体上のK-rasより10cM遠位にありK-ras intron内に欠失が存在することも明らかにした(野村、加藤)。 4)藤堂は、紫外線による損傷を持つDNAに特異的に結合する蛋白を2種見い出した。1つは(6-4)光産物に対する光回復酵素で、酵素蛋白の精製に成功し、この酵素が損傷DNAを元に形に修復する活性を持つ事を明らかにした。

Research Products

(27 results)

All Other

All Publications (27 results)

[Publications] Todo,T: "High-level expression of the photorepair gene in Drosophila ovary and its evolutionary implications." Mutat.Res.315. 213-228 (1994)
[Publications] Kato,T: "Cloning of a marsupial DNA photolyase gene and the lack of related nucleotide sequences in placental mammals." Nucl.Acids Res.,. 22. 4119-4124 (1994)
[Publications] Nakajima,H.: "Enhancement of tumor growth under short light/dark cycle in the mouse lung." Cancer Letters. 78. 127-131 (1994)
[Publications] Mizutani,T: "Identification of estrogen receptorin human adipose tissue and adipocytes." J.Clin.Endocrinol.Metab.78. 950-954 (19094)
[Publications] Ohsugi,T.: "Engraftment of HTLV-1-ransformed human T-cell line into SCID mice with NK cell function." J.Vet.Med.Sci.56. 601-603 (1994)
[Publications] Enomoto,T.: "Analysis of clonality by amplification of short tandem repeats." Diag.Mol.Pathol.3. 292-297 (1994)
[Publications] Fujita,M.: "Alteration of the p53 tumor suppressor gene occurs independently of K-ras activation and more frequently in serous adenocarcinomas than in other common epithelial tumors of the human ovary." Jpn.J.Cancer.Res.85. 1247-1256 (1994)
[Publications] Enomoto,T.: "Loss of expression and loss of heterozygosity in the DCC gene in neoplasms of the human female reproductive tract." Brit.J.Cancer. (印刷中). (1995)
[Publications] Enomoto,T.: "Alteration of the p53 tumor supperssor gene and activation of c-K-ras-2 protooncogene in endometrial adenocarcinoma from Colorado." Anat.Pathology. (印刷中). (1995)
[Publications] Yoshimoto,Y.: "External and internal comparisons of mortality among the offspring of atomic bomb survivors." Cancer Detection and Prevention:19/Issue 1. 49(印刷中). (1995)
[Publications] Yoshimoto,Y.: "In-utero exposed atomic bomb survivors:cancer risk update." Lancet. 344. 345-346 (1994)
[Publications] Mabuchi,K.: "Cancer incidence in atomic bomb survivors.Part 1:Use of the tumor registries in Hiroshima and Nagasaki." Radiat.Res.137. S1-S16 (1994)
[Publications] Sasaki,M.S.: "Dissociation between radioresistant DNA replicasion and chromosomal radiosensitivity in ataxia telangiectasia." Mutation Res.307. 107-113 (1994)
[Publications] Kato,M.V.: "Parental origin of germ-line and somatic mutations in the retinoblastoma gene." Hum.Genet.94. 31-38 (1994)
[Publications] Kato,M.V.: "Mutations in the retinoblastoma gene and their expression in somatic cells of patients with hereditary retinoblastoma." Hum.Mutat.3. 44-51 (1994)
[Publications] Katoh,H.: "Segmental tetrasomy of chromosome 12 in the mouse." Cytotenet.Cell.Genet.67. 27-30 (1994)
[Publications] Horie,H.: "Transgenic mice carrying the human poliovirus receptor:New animal model for study of poliovirus neurovirulence." J.Viro.68(2). 681-688 (1994)
[Publications] Sakurai,T.: "The ter primordial germ cell deficiency mutation maps near Grl-1 on mouse chromosome 18." Mammalian Genome. 5. 333-336 (1994)
[Publications] Shimizu,T.: "Detection of mutations of the RB1 gene in retinoblastoma patients by using exon-by-exon PCR-SSCP analysis." Am.J.Hum.Genet.54. 793-800 (1994)
[Publications] 野村大成: "がん偶感-実験医学と疫学" Oncologia. 27. 162- (1994)
[Publications] 野村大成: "放射線被曝による継世代発がん" INNERVISION. 9:. 11- (1994)
[Publications] 渡辺敦光: "親の受けた遺伝子の傷が子孫に伝播するか-マウス肝腫瘍をモデルとして-" 広島医学. 47. 396-399 (1994)
[Publications] Nomura,T.: "Male-mediated Developmental Toxicity" Plenum Press,New York, 11 (1994)
[Publications] Katoh,H.: "Genetics in wild mice-Applications for biomedical reserch" Japanese Scientific Societies Press, 15 (1994)
[Publications] Toichi,E.: "In the SAM Model of Senescence" Elsevier Science B.V., 6 (1994)
[Publications] Hanada,K.: "In the SAM Model of Senescence" Elsevier Science B.V., 4 (1994)
[Publications] 野村大成: "マウスと私" 学士会, 5 (1994)

1994 Fiscal Year Annual Research Report

放射線被爆による継世代発がん

Principal Investigator

藤堂 剛 大阪大学, 医学部 (90163948)

Research Products

[Publications] Todo,T: "High-level expression of the photorepair gene in Drosophila ovary and its evolutionary implications." Mutat.Res.315. 213-228 (1994)

[Publications] Kato,T: "Cloning of a marsupial DNA photolyase gene and the lack of related nucleotide sequences in placental mammals." Nucl.Acids Res.,. 22. 4119-4124 (1994)

[Publications] Nakajima,H.: "Enhancement of tumor growth under short light/dark cycle in the mouse lung." Cancer Letters. 78. 127-131 (1994)

[Publications] Mizutani,T: "Identification of estrogen receptorin human adipose tissue and adipocytes." J.Clin.Endocrinol.Metab.78. 950-954 (19094)

[Publications] Ohsugi,T.: "Engraftment of HTLV-1-ransformed human T-cell line into SCID mice with NK cell function." J.Vet.Med.Sci.56. 601-603 (1994)

[Publications] Enomoto,T.: "Analysis of clonality by amplification of short tandem repeats." Diag.Mol.Pathol.3. 292-297 (1994)

[Publications] Fujita,M.: "Alteration of the p53 tumor suppressor gene occurs independently of K-ras activation and more frequently in serous adenocarcinomas than in other common epithelial tumors of the human ovary." Jpn.J.Cancer.Res.85. 1247-1256 (1994)

[Publications] Enomoto,T.: "Loss of expression and loss of heterozygosity in the DCC gene in neoplasms of the human female reproductive tract." Brit.J.Cancer. (印刷中). (1995)

[Publications] Enomoto,T.: "Alteration of the p53 tumor supperssor gene and activation of c-K-ras-2 protooncogene in endometrial adenocarcinoma from Colorado." Anat.Pathology. (印刷中). (1995)

[Publications] Yoshimoto,Y.: "External and internal comparisons of mortality among the offspring of atomic bomb survivors." Cancer Detection and Prevention:19/Issue 1. 49(印刷中). (1995)

[Publications] Yoshimoto,Y.: "In-utero exposed atomic bomb survivors:cancer risk update." Lancet. 344. 345-346 (1994)

[Publications] Mabuchi,K.: "Cancer incidence in atomic bomb survivors.Part 1:Use of the tumor registries in Hiroshima and Nagasaki." Radiat.Res.137. S1-S16 (1994)

[Publications] Sasaki,M.S.: "Dissociation between radioresistant DNA replicasion and chromosomal radiosensitivity in ataxia telangiectasia." Mutation Res.307. 107-113 (1994)

[Publications] Kato,M.V.: "Parental origin of germ-line and somatic mutations in the retinoblastoma gene." Hum.Genet.94. 31-38 (1994)

[Publications] Kato,M.V.: "Mutations in the retinoblastoma gene and their expression in somatic cells of patients with hereditary retinoblastoma." Hum.Mutat.3. 44-51 (1994)

[Publications] Katoh,H.: "Segmental tetrasomy of chromosome 12 in the mouse." Cytotenet.Cell.Genet.67. 27-30 (1994)

[Publications] Horie,H.: "Transgenic mice carrying the human poliovirus receptor:New animal model for study of poliovirus neurovirulence." J.Viro.68(2). 681-688 (1994)

[Publications] Sakurai,T.: "The ter primordial germ cell deficiency mutation maps near Grl-1 on mouse chromosome 18." Mammalian Genome. 5. 333-336 (1994)

[Publications] Shimizu,T.: "Detection of mutations of the RB1 gene in retinoblastoma patients by using exon-by-exon PCR-SSCP analysis." Am.J.Hum.Genet.54. 793-800 (1994)

[Publications] 野村大成: "がん偶感-実験医学と疫学" Oncologia. 27. 162- (1994)

[Publications] 野村大成: "放射線被曝による継世代発がん" INNERVISION. 9:. 11- (1994)

[Publications] 渡辺敦光: "親の受けた遺伝子の傷が子孫に伝播するか-マウス肝腫瘍をモデルとして-" 広島医学. 47. 396-399 (1994)

[Publications] Nomura,T.: "Male-mediated Developmental Toxicity" Plenum Press,New York, 11 (1994)

[Publications] Katoh,H.: "Genetics in wild mice-Applications for biomedical reserch" Japanese Scientific Societies Press, 15 (1994)

[Publications] Toichi,E.: "In the SAM Model of Senescence" Elsevier Science B.V., 6 (1994)

[Publications] Hanada,K.: "In the SAM Model of Senescence" Elsevier Science B.V., 4 (1994)

[Publications] 野村大成: "マウスと私" 学士会, 5 (1994)

藤堂剛大阪大学, 医学部 (90163948)