1991 Fiscal Year Annual Research Report

発がんのイニシェ-ションとその阻害

Research Project

Project/Area Number	03151042
Research Institution	Okayama University
Principal Investigator	早津彦哉岡山大学, 薬学部, 教授 (10012593)
Co-Investigator(Kenkyū-buntansha)	菊川清見東京薬科大学, 教授 (90120146) 大西克成徳島大学, 医学部, 教授 (10037400) 山添康慶應義塾大学, 医学部, 助教授 (00112699) 長尾美奈子国立がんセンター, 研究所, 部長 (40100151) 根岸和雄岡山大学, 遺伝子実験施設, 助教授 (70116490)
Keywords	発がんイニシエ-タ- / クロロフィル / DNA組換え / 太陽性 / p53遺伝子 / スルホトランスフェラ-ゼ / 胆道がん / カ-ボンラジカル
Research Abstract	最近、ヒト発がんの原因が環境因子による突然変異である例が、アフラトキシンB_1誘発肝がんや紫外線誘発皮膚がんにおけるp53遺伝子の変異で示されている。これらの発見にはイニシエ-タ-の変異誘発機構のin vitroでの研究が重要な役割を果たしている.一方、がん予防の観点からは、イニシエ-タ-作用阻害因子を見出し、その機構を明らかにすることが重要である。この両者について各班員が、各々独自の手段を用いて研究を行い、興味ある成果を出している. 早津彦哉は、イニシエ-タ-としてのTrpーPー2の作用とその阻害について研究した。TrpーPー2は培養細胞に対してS9存在下で突然変異を起すがS9なしでも小核形成をひき起こすことを見出した。またクロロフィルとその種々の誘導体がTrpーPー2の遺伝子毒性を阻害し、その機構は複合体形成と、ある場合には化学分解を伴うTrpーPー2捕捉作用に由来することを明らかにした。また緑茶成分エピガロカテキンガレ-トは亜硝酸を捕捉しニトロサミン生成反応を強く阻害することを示した。池田日出男は、動物細胞由来の無細胞DNA組換えの新しい系を開発した.根岸和雄は、太陽光によるM13mp2ファ-ジの変異を研究し、主にGからCへのトランスバ-ジョンが起きることを明らかにした。長尾美奈子は、IQで誘発したラットのジンバ-ル腺腫のp53遺伝子の変異位置を特定し、Gの変異が主として起っていることを見出した。山添康は、ヒト肝のスルホトランスフェラ-ゼが複数存在すること、そのうちの特定の種によって、GluーPー1(NHOH)の硫酸エステル化が起ることを明らかにした。大西克成は、ヒト膵管胆道合流異常症での胆道発がんのイニシエ-ションについて調べ、膵液による脱抱合反応が重要であることを見出した。菊川清見は、フェノ-ル性医薬品から亜硝酸との反応で生じるジアゾキノン体がDNAを損傷する機構を調べ、カ-ボンラジカルが原因であることを示した。

Research Products

(15 results)

All Other

All Publications (15 results)

[Publications] Sakae Arimoto: "Formation of 2-amino-3-methylimidazo[4,5-f]quinoline,a directly mutagnic product,by near-ultraviolet irradiation of a mixture of 2-amino-3-methylimidazo[4,5-f]quinoline and N-nitrodimethylamine." Mutation Research. 252. 161-167 (1991)
[Publications] Hikoya Hayatsu(ed.by H.Hayatsu): "Methods for separation and detection of heterocyclic amines." Mutagens in Food:Detection and Prevention. 101-112 (1991)
[Publications] Hikoya Hayatsu: "Suppression of genotoxicity of carcinogens by (-)epigallocatechin gallate." Preventive Medicine.
[Publications] Michiyo Kumagai: "Molecular analysis of the recombination junctions of 1 bio transducing Phages." Molecular and General Genetics. 230. 60-64 (1991)
[Publications] Hideo Ikeda(ed.by T.Ando): "Involvement of type II DNA topoisomerase in illegitimate recombination in Escherichia coli:Analysis of the partial diploid of phage T4 and the specialized transducing particles of phage 1." DNA topoisomerases in chemotherpy.
[Publications] Yasushi Yamazoe(eds.by L.Ernster et al.): "Acetyltransferase and sulfotransferase which activate mutagens and carcinogens through O-esterification mechanisms." Xenobiotics and Cancer Imprications for Chemical Carcinogenesis and Cancer Chemotherapy. 109-117 (1991)
[Publications] D.Gong: "Purification of hepatic N-hydroxyarylamine sulfotransferases and their regulation by growth hormone and thyroid hormone in rats." Journal of Biochemistry. 110. 226-231 (1991)
[Publications] M.Suzuki: "Inhibitory effect of 2-O-octadecylascorbic acid in agglutination assay with concanavalin A;short-term examination of rat urinary-bladder carcinogenesis." Japanese Journal of Cancer Research. 82. 286-289 (1991)
[Publications] Hiroshi Makino: "Rat p53 gene mutations in primary Zymbal gland tumors induced by IQ,a food mutagen." Proceedings of the National Academy of Sciences.
[Publications] Tetsuya Yashiki: "Inhibition of DNA chain elongation by a phosphotriester linkage in template oligodeoxyribonucleotides." Nucleic Acids Symposium Series. 25. 25-26 (1991)
[Publications] Keiko Matsumoto: "Nucleotide sequence analysis of phage M13mp2 mutants produced from transfection of phage DNA having N^4-aminocytosines at defined sequence positions.Proof that a base change occurs on the base-analog." Mutation Research.
[Publications] Tetsuta Kato: "Loss of heterocyclic amine mutagens by insoluble hemicellulose fiber and high-molecular-weight soluble polyphenolics of coffee." Mutation Research. 246. 169-178 (1991)
[Publications] Tetsuta Kato: "DNA strand breakage by hydroxyphenyl radicals generated from mutagenic diazoquinoe compounds." Mutation Research.
[Publications] Keiko Kataoka: "Species differences in metabolic activation and inactivation of 1-nitropyrene in the liver." Cancer Research. 51. 3919-3924 (1991)
[Publications] Yoshinari Ohnishi(eds.by M.Cooke et al.): "Metabolic formation and inactivation of 1-nitropyrene oxides and the effect of pyrene on the formation of 1-nitropyrene metabolites." Polynuclear Aromatic Hydrocarbons:Measurements,Means,and Metabolites. 641-655 (1991)

1991 Fiscal Year Annual Research Report

発がんのイニシェ-ションとその阻害

Principal Investigator

早津 彦哉 岡山大学, 薬学部, 教授 (10012593)

Research Products

[Publications] Sakae Arimoto: "Formation of 2-amino-3-methylimidazo[4,5-f]quinoline,a directly mutagnic product,by near-ultraviolet irradiation of a mixture of 2-amino-3-methylimidazo[4,5-f]quinoline and N-nitrodimethylamine." Mutation Research. 252. 161-167 (1991)

[Publications] Hikoya Hayatsu(ed.by H.Hayatsu): "Methods for separation and detection of heterocyclic amines." Mutagens in Food:Detection and Prevention. 101-112 (1991)

[Publications] Hikoya Hayatsu: "Suppression of genotoxicity of carcinogens by (-)epigallocatechin gallate." Preventive Medicine.

[Publications] Michiyo Kumagai: "Molecular analysis of the recombination junctions of 1 bio transducing Phages." Molecular and General Genetics. 230. 60-64 (1991)

[Publications] Hideo Ikeda(ed.by T.Ando): "Involvement of type II DNA topoisomerase in illegitimate recombination in Escherichia coli:Analysis of the partial diploid of phage T4 and the specialized transducing particles of phage 1." DNA topoisomerases in chemotherpy.

[Publications] Yasushi Yamazoe(eds.by L.Ernster et al.): "Acetyltransferase and sulfotransferase which activate mutagens and carcinogens through O-esterification mechanisms." Xenobiotics and Cancer Imprications for Chemical Carcinogenesis and Cancer Chemotherapy. 109-117 (1991)

[Publications] D.Gong: "Purification of hepatic N-hydroxyarylamine sulfotransferases and their regulation by growth hormone and thyroid hormone in rats." Journal of Biochemistry. 110. 226-231 (1991)

[Publications] M.Suzuki: "Inhibitory effect of 2-O-octadecylascorbic acid in agglutination assay with concanavalin A;short-term examination of rat urinary-bladder carcinogenesis." Japanese Journal of Cancer Research. 82. 286-289 (1991)

[Publications] Hiroshi Makino: "Rat p53 gene mutations in primary Zymbal gland tumors induced by IQ,a food mutagen." Proceedings of the National Academy of Sciences.

[Publications] Tetsuya Yashiki: "Inhibition of DNA chain elongation by a phosphotriester linkage in template oligodeoxyribonucleotides." Nucleic Acids Symposium Series. 25. 25-26 (1991)

[Publications] Keiko Matsumoto: "Nucleotide sequence analysis of phage M13mp2 mutants produced from transfection of phage DNA having N^4-aminocytosines at defined sequence positions.Proof that a base change occurs on the base-analog." Mutation Research.

[Publications] Tetsuta Kato: "Loss of heterocyclic amine mutagens by insoluble hemicellulose fiber and high-molecular-weight soluble polyphenolics of coffee." Mutation Research. 246. 169-178 (1991)

[Publications] Tetsuta Kato: "DNA strand breakage by hydroxyphenyl radicals generated from mutagenic diazoquinoe compounds." Mutation Research.

[Publications] Keiko Kataoka: "Species differences in metabolic activation and inactivation of 1-nitropyrene in the liver." Cancer Research. 51. 3919-3924 (1991)

[Publications] Yoshinari Ohnishi(eds.by M.Cooke et al.): "Metabolic formation and inactivation of 1-nitropyrene oxides and the effect of pyrene on the formation of 1-nitropyrene metabolites." Polynuclear Aromatic Hydrocarbons:Measurements,Means,and Metabolites. 641-655 (1991)

早津彦哉岡山大学, 薬学部, 教授 (10012593)