1991 年度実績報告書

環境要因の人体影響ー人体影響に関与する遺伝的要因

研究課題

研究課題/領域番号	03202138
研究機関	京都府立医科大学
研究代表者	阿部達生京都府立医科大学, 医学部, 教授 (60079746)
研究分担者	杉山武敏京都大学, 医学部, 教授 (20030851) 西村泰治九州大学, 生体防衛医学研究所, 助教授 (10156119) 野村大成大阪大学, 医学部, 教授 (90089871) 島昭紘東京大学, 理学部, 教授 (60011590) 池永満生京都大学, 放射線生物研究センター, 教授 (70025378)
キーワード	FISH / P‐450 / MNNG / トランジション / HLA‐DRα鎖遺伝子 / 間期死反応 / 生存突然変異
研究概要	本年度の研究成果を以下に要約して述べる. 1)化学物質(ビオチン等)標識/蛍光シグナル検出の組合せによるfluorescent in situ hybridization(FISH)法を開発し,環境要因によるDNA損傷を修復する酵素MGMTと多型の存在が知られている薬物代謝酵素P‐450分子種CYP3A4遺伝子の座をそれぞれ10q26と7q22.1と決定した. 2)大腸菌のcrp(cAMP receptor protein)遺伝子を含むプラスミドpHA7をMNNGで処理し、宿主大腸菌にトランスフェクションして,crp^+からcrp^-への突然変異を生じた変異株コロニ-44個分離した.それぞれの変異株からプラスミドを回収し,M13ファ-ジに再クロ-ニングした後,crp遺伝子(627 塩基対)の全塩基配列をサンガ-法で決定した.全部で42個の塩基配列を検出したが,うち,41個は塩基置換で, すべてがトランジション型であった。この結果は,MNNGによってDNAに生じたO^6‐メチルグアニンがDNA複製に際して誤ってチミンと対合することが,MNNG誘発突然変異の主要な原因であることを強く示唆した.3)免疫応答を惹起する環境要因である抗原への暴露,また珪肺症の原因である遊離珪酸への暴露に対する生体側の反応に及ぼすHLA遺伝子の影響を個体レベルで解析するためのモデル動物として,HLAーDRα鎖遺伝子導入マウスを作製した.4)開発した間期死反応検出系で約50種の近交系マウスに0.01‐0.05Gyの微量のX線を照射し,間期死反応を観察した.細胞死は,X線量に比例しほぼ直線的に増加するが,マウス系統間に大きな差のあることがわかった.5)メダカb座位に関する誘発生存突然変異について,同座位に関する既知の7つのalleleを基準とした機能的マッピングを行った.10個のENU誘発生存突然変異と6個のγ線誘発生存突然変異をまず同型接合化した.ENU誘発生存突然変異は,すべてhomozygous viableであった.

研究成果
(21件)

すべてその他

すべて文献書誌 (21件)

[文献書誌] Inazawa J,Abe T,et al: "Assignment of the human granulocyte colony stimulating factor receptor gene(CSF3R)to chromosome 1 at region p35ーp34.3." Genomics. 10. 1075-1078 (1991)
[文献書誌] Sonoda,Y Abe T,et al: "Treatment of idiopathic neutropenia in the elderly with recombinant human granulocyte colony‐stimulating factor." Acta Haematol. 85. 146-152 (1991)
[文献書誌] Nishi M,Abe T,et al: "Regional chromosomal assignment of carcinoembryonic antigen gene(CEA)to chromosome 19 at band q13.2." Cancer Genet Cytogenet. 54. 77-81 (1991)
[文献書誌] Kubonishi I,Abe T,et al: "Novel t(15;19)(q15;p13)chromosome abnormality in a thymic carcinoma." Cancer. 51. 3327-3328 (1991)
[文献書誌] Sonoda Y,Abe T,et al: "Action of human interleukin‐4/B‐cell stimulatory factor on proliferation and differentiation of enriched hematopoietic progenitor cells in culture." Blood. 75. 1615-1621 (1990)
[文献書誌] Ohe T,Abe T,et al: "cis‐diamminodichloroplatinum(II)‐induced sister chromatid exchanges and chromosome aberration formation in cultured human lymphocytes and their inhibition by sodium thiosulfate." Mutatin Res. 244. 279-285 (1990)
[文献書誌] Isowa G,Ikenaga M,et al: "O^6‐Methylguanine‐DNA methyltransferase activity in human liver tumors." Carcinogenesis. 12. 1313-1317 (1991)
[文献書誌] Wang Y,Ikenaga M,et al: "Assignment of a chinese xeroderma pigmentosum patient from Taiwan to complementation group C." J Radiat Res. 32. 181-190 (1991)
[文献書誌] Takimoto K,Ikenaga M,et al: "Specificity of mutational DNA sequence changes induced by X‐rays in the cloned Escherichia coli crp gene." Mutation Res. 254. 199-206 (1991)
[文献書誌] Habuchi T.Sugiyama T et al: "Allelic loss of chromosome 17p is strongly associated with invasive cancer." Jap J Cancer Res.
[文献書誌] Ogawa O.Sugiyama T,et al: "Allelic loss at chromosome 3p characterizes clear cell phenotype of renal cell carcinoma." Cancer Res. 51. 949-953 (1991)
[文献書誌] Shima S,et al: "Development of a possible nonmammalian test system for radiation‐induced germ‐cell mutagenesis using a fish,the Japanese Medaka(Oryzias latipes)." Proc Natl Acad Sci USA. 88. 2545-2549 (1991)
[文献書誌] Kubota Y,Shima S,et al: "Comparative study fo embrvonic thermoresistance of two inbred strains of the Medaka(Oryzias latipes)." J Comp Physiol B. 160. 621-625 (1991)
[文献書誌] Nomura T,et al: "Programmed cell death in whole body and organ systems by low dose radiation." J Radiat Res.
[文献書誌] Nomura T,et al: "Rapid growth and spontaneous meastasis of human germinal tumors ectopically transplanted into scid(Severe Combined Immunodeficiency)and scid‐streaker mice." Jpn J Cancer Res. 82. 701-709 (1991)
[文献書誌] Ishikawa J,Maeda S,et al: "Inactivation of the retinoblastoma gene in human bladder and renal cell carcinomas." Cancer Res.
[文献書誌] Fujisawa K,Nishimura Y,et al: "High precursor frequencv of human T cells reactive to HLA‐DQ molecules expressed on mouse L cell transfectants." Eur J Jmmunol.
[文献書誌] Kamikawaji N.Nishimura Y,et al: "HLA‐DQ restricted CD4^+ T cells specific to streptococcal antigen exist in low responders but not in high responders." J Immunol. 146. 2560-2567 (1991)
[文献書誌] Abe T: "造血器腫瘍アトラス,‐形態,免疫,染色体と遺伝子.単行本(編著書)" 日本医事新報社, 1-162 (1991)
[文献書誌] Abe T: "遺伝子診断‐原理・方法と臨床応用.単行本(訳書)" 金芳堂, 1-321 (1991)
[文献書誌] Itokawa Y: "Magnesium in health and disease." John Libbey&Co.,Ltd., (1989)

1991 年度 実績報告書

環境要因の人体影響ー人体影響に関与する遺伝的要因

研究代表者

阿部 達生 京都府立医科大学, 医学部, 教授 (60079746)

研究成果

[文献書誌] Inazawa J,Abe T,et al: "Assignment of the human granulocyte colony stimulating factor receptor gene(CSF3R)to chromosome 1 at region p35ーp34.3." Genomics. 10. 1075-1078 (1991)

[文献書誌] Sonoda,Y Abe T,et al: "Treatment of idiopathic neutropenia in the elderly with recombinant human granulocyte colony‐stimulating factor." Acta Haematol. 85. 146-152 (1991)

[文献書誌] Nishi M,Abe T,et al: "Regional chromosomal assignment of carcinoembryonic antigen gene(CEA)to chromosome 19 at band q13.2." Cancer Genet Cytogenet. 54. 77-81 (1991)

[文献書誌] Kubonishi I,Abe T,et al: "Novel t(15;19)(q15;p13)chromosome abnormality in a thymic carcinoma." Cancer. 51. 3327-3328 (1991)

[文献書誌] Sonoda Y,Abe T,et al: "Action of human interleukin‐4/B‐cell stimulatory factor on proliferation and differentiation of enriched hematopoietic progenitor cells in culture." Blood. 75. 1615-1621 (1990)

[文献書誌] Ohe T,Abe T,et al: "cis‐diamminodichloroplatinum(II)‐induced sister chromatid exchanges and chromosome aberration formation in cultured human lymphocytes and their inhibition by sodium thiosulfate." Mutatin Res. 244. 279-285 (1990)

[文献書誌] Isowa G,Ikenaga M,et al: "O^6‐Methylguanine‐DNA methyltransferase activity in human liver tumors." Carcinogenesis. 12. 1313-1317 (1991)

[文献書誌] Wang Y,Ikenaga M,et al: "Assignment of a chinese xeroderma pigmentosum patient from Taiwan to complementation group C." J Radiat Res. 32. 181-190 (1991)

[文献書誌] Takimoto K,Ikenaga M,et al: "Specificity of mutational DNA sequence changes induced by X‐rays in the cloned Escherichia coli crp gene." Mutation Res. 254. 199-206 (1991)

[文献書誌] Habuchi T.Sugiyama T et al: "Allelic loss of chromosome 17p is strongly associated with invasive cancer." Jap J Cancer Res.

[文献書誌] Ogawa O.Sugiyama T,et al: "Allelic loss at chromosome 3p characterizes clear cell phenotype of renal cell carcinoma." Cancer Res. 51. 949-953 (1991)

[文献書誌] Shima S,et al: "Development of a possible nonmammalian test system for radiation‐induced germ‐cell mutagenesis using a fish,the Japanese Medaka(Oryzias latipes)." Proc Natl Acad Sci USA. 88. 2545-2549 (1991)

[文献書誌] Kubota Y,Shima S,et al: "Comparative study fo embrvonic thermoresistance of two inbred strains of the Medaka(Oryzias latipes)." J Comp Physiol B. 160. 621-625 (1991)

[文献書誌] Nomura T,et al: "Programmed cell death in whole body and organ systems by low dose radiation." J Radiat Res.

[文献書誌] Nomura T,et al: "Rapid growth and spontaneous meastasis of human germinal tumors ectopically transplanted into scid(Severe Combined Immunodeficiency)and scid‐streaker mice." Jpn J Cancer Res. 82. 701-709 (1991)

[文献書誌] Ishikawa J,Maeda S,et al: "Inactivation of the retinoblastoma gene in human bladder and renal cell carcinomas." Cancer Res.

[文献書誌] Fujisawa K,Nishimura Y,et al: "High precursor frequencv of human T cells reactive to HLA‐DQ molecules expressed on mouse L cell transfectants." Eur J Jmmunol.

[文献書誌] Kamikawaji N.Nishimura Y,et al: "HLA‐DQ restricted CD4^+ T cells specific to streptococcal antigen exist in low responders but not in high responders." J Immunol. 146. 2560-2567 (1991)

[文献書誌] Abe T: "造血器腫瘍アトラス,‐形態,免疫,染色体と遺伝子.単行本(編著書)" 日本医事新報社, 1-162 (1991)

[文献書誌] Abe T: "遺伝子診断‐原理・方法と臨床応用.単行本(訳書)" 金芳堂, 1-321 (1991)

[文献書誌] Itokawa Y: "Magnesium in health and disease." John Libbey&Co.,Ltd., (1989)

1991 年度実績報告書

阿部達生京都府立医科大学, 医学部, 教授 (60079746)