1998 年度実績報告書

ヒト培養細胞の突然変異誘発を促進する膵癌患者血清因子

研究課題

研究課題/領域番号	09671209
研究機関	千葉大学
研究代表者	山森秀夫千葉大学, 医学部, 講師 (00166836)
研究分担者	田代亜彦千葉大学, 医学部, 助教授 (70143310) 鈴木信夫千葉大学, 医学部, 教授 (90111426)
キーワード	膵癌 / K-ras / 突然変異 / プロテアーゼ / 血清因子
研究概要	膵癌組織においてはK-ras codon12の点突然変異が非常に高頻度で検出されるが,私共はその変異を促進する因子が膵癌患者血清中に存在することを報告してきた。今回は,膵癌組織培養細胞が同様な因子を試験管内で産生放出しているか否かを検討した。膵癌組織培養細胞から無血清培地を採取し,その培地成分を塩析と色素樹脂カラムクロマトグラフィーにより分離分画した。次に,まずその画分液の中から健康人のリンパ球系細胞におけるプロテアーゼ誘発活性を促進するものを選択した。引き続き高頻度の突然変異が誘導され得るヒト細胞株を培養し,紫外線照射後ウアバイン耐性化変異の頻度を測定した.さらに,この形質変異の誘導を促進する画分についてPCRとdot-blot hybridization法を用いてK-ras codon12変異の誘導も促進することを検証した。調査した膵癌組織培養細胞株全ての培養上清中に,以上の変異促進活性のあることが判明した。以上の結果から,膵癌組織におけるK-ras codon12の高頻度変異の原因として,癌組織細胞から放出される因子により変異誘導が促進されるという変異発生の新しいメカニズムが示唆された。

研究成果
(11件)

すべてその他

すべて文献書誌 (11件)

[文献書誌] Isogai,E,Ishijima,S.,Sonoda,T.,Kita,K.,Suzuki,H.,Hasegawa,R.,Yamamori,H.,Takakubo,Y.,and Suzuki,N.: "Protease activation following UV and inradiation is linked to hypomutability in human cells selected for resistance to combiuatiou of UV antipain." Mutation Res.403. 215-222 (1998)
[文献書誌] Sugita,K,Suzuki,N.,Higuchi,Y.,Kita,K.,Suzuki,Y.,and Lehmann A.: "Enhancement of XP-G mRNA expression by human interferon-β in Cockayne syndrome cells." Mutation Res.408. 67-72 (1998)
[文献書誌] Suzuki,H,Watanabe,M.,Wu,Y.,Sugita,T.,Kita,K.,Sato,T.,Wang,X.,Tanzawa,H.,Sekiya,S.and Suzuki,N.: "Mutagenicity of microcystin-LR in human RSa cells." International Journal of Molecular Medicine. 2. 109-112 (1998)
[文献書誌] Higuchi,Y,Kita,K.,Nakanishi,H.,Wang,XL.,Sugaya,S.,Tanzawa,H.,Yamamori,H.,Sugita,K.Yamaura A.and Suzuki,N.: "Search for genes involved in UV-resistance in human cells by mRNA differential display:increased transcriptional expression of nucleophosmin and T-plastin genes in association with the resistance." BBRC. 248. 597-602 (1998)
[文献書誌] Suzuki,N.,Ishibashi,M.,Kita,K.,Wu,Y.,Nomura,J.,Takakukbo,Y.,Hiroshima,K.,Genga,K.,Ohwada,H.and Hayashi,Y.: "Detection of Serum Factors Enhancing Cell Mutability From Lung Cancer Patients by Application of Hypermutable Human RS Cells." Int.J.Cancer. 78. 550-555 (1998)
[文献書誌] Wu,Y.,Hiwasa,T,Isogai,E.,Sonoda,T.,Kita,K.,Chen,Z.,Sugaya,S.,Yamamori,H.,Takazawa,H.and Suzuki,N.: "Activation of MAP kinases by 5-fluorouracil in a 5-fluorouracil-resistant variant human cell line derived from a KT breast cancer cell line." Int.J.Oncol.13. 1241-1245 (1998)
[文献書誌] Kikuno,K.,Kita,K.,Nomura,J.,Hiwasa,T.,Yonemitsu,H.and Suzuki,N.: "Search for genes responsible for UV susceptibility of human cells:involvment of syndecan-1 in UV resistance." Biochem.Biophys.Res.Commun.253. 519-523 (1998)
[文献書誌] Tsuguhiko Tashiro,Hideo Yamamori,Kazuya Takagi,Naganori Hayashi,Toshiyuki Sugiura,and Nobuyuki Nakajima.: "The effect of newly devel oped fat emulsion containing eicosapentaenoic acid and docosahexaenoic acid on fatty acid profiles in rats." Nutrition. 14. 372-375 (1998)
[文献書誌] Tsuguhiko Tashiro,H.Yamamori,N.Hayashi,K.Furukawa,Y.Morishima,T.Sugiura,T.Itabashi,W.Sano,Y.Toyoda,H.Nitta,J.Hirano,K.Nishiya and N.Nakajima,M.D.: "N-3 versus N-6 polyunsaturated fatty ascids(PUFA) in critical illness." Nutrition. 14. 551-553 (1998)
[文献書誌] Hayashi,T.Tashiro,H.Yamamori,K.Furukawa,Y.Morishima,T.Sugiura,T.Itabashi,W.Sano,Y.Toyoda,H.Nitta,J.Hirano,K.Nishiya and N.Nakajima.: "Effect of intravenous n-3 and n-6 fat emulsion and delayed type hypersensitivity in burned rats receiving total parenteral nutrition." J Parent Ent Nutr.22. 363-367 (1998)
[文献書誌] T.Tashiro,Ishiodori K,H.Yamamori,Takagi K,Nakajima N.: "Glucose oxidation in critically ill patients measured with stable isotope and indirect calorimetry" Chiba Med J.74. 393-399 (1998)

1998 年度 実績報告書

ヒト培養細胞の突然変異誘発を促進する膵癌患者血清因子

研究代表者

山森 秀夫 千葉大学, 医学部, 講師 (00166836)

研究成果

[文献書誌] Isogai,E,Ishijima,S.,Sonoda,T.,Kita,K.,Suzuki,H.,Hasegawa,R.,Yamamori,H.,Takakubo,Y.,and Suzuki,N.: "Protease activation following UV and inradiation is linked to hypomutability in human cells selected for resistance to combiuatiou of UV antipain." Mutation Res.403. 215-222 (1998)

[文献書誌] Sugita,K,Suzuki,N.,Higuchi,Y.,Kita,K.,Suzuki,Y.,and Lehmann A.: "Enhancement of XP-G mRNA expression by human interferon-β in Cockayne syndrome cells." Mutation Res.408. 67-72 (1998)

[文献書誌] Suzuki,H,Watanabe,M.,Wu,Y.,Sugita,T.,Kita,K.,Sato,T.,Wang,X.,Tanzawa,H.,Sekiya,S.and Suzuki,N.: "Mutagenicity of microcystin-LR in human RSa cells." International Journal of Molecular Medicine. 2. 109-112 (1998)

[文献書誌] Suzuki,N.,Ishibashi,M.,Kita,K.,Wu,Y.,Nomura,J.,Takakukbo,Y.,Hiroshima,K.,Genga,K.,Ohwada,H.and Hayashi,Y.: "Detection of Serum Factors Enhancing Cell Mutability From Lung Cancer Patients by Application of Hypermutable Human RS Cells." Int.J.Cancer. 78. 550-555 (1998)

[文献書誌] Wu,Y.,Hiwasa,T,Isogai,E.,Sonoda,T.,Kita,K.,Chen,Z.,Sugaya,S.,Yamamori,H.,Takazawa,H.and Suzuki,N.: "Activation of MAP kinases by 5-fluorouracil in a 5-fluorouracil-resistant variant human cell line derived from a KT breast cancer cell line." Int.J.Oncol.13. 1241-1245 (1998)

[文献書誌] Kikuno,K.,Kita,K.,Nomura,J.,Hiwasa,T.,Yonemitsu,H.and Suzuki,N.: "Search for genes responsible for UV susceptibility of human cells:involvment of syndecan-1 in UV resistance." Biochem.Biophys.Res.Commun.253. 519-523 (1998)

[文献書誌] Tsuguhiko Tashiro,Hideo Yamamori,Kazuya Takagi,Naganori Hayashi,Toshiyuki Sugiura,and Nobuyuki Nakajima.: "The effect of newly devel oped fat emulsion containing eicosapentaenoic acid and docosahexaenoic acid on fatty acid profiles in rats." Nutrition. 14. 372-375 (1998)

[文献書誌] Tsuguhiko Tashiro,H.Yamamori,N.Hayashi,K.Furukawa,Y.Morishima,T.Sugiura,T.Itabashi,W.Sano,Y.Toyoda,H.Nitta,J.Hirano,K.Nishiya and N.Nakajima,M.D.: "N-3 versus N-6 polyunsaturated fatty ascids(PUFA) in critical illness." Nutrition. 14. 551-553 (1998)

[文献書誌] T.Tashiro,Ishiodori K,H.Yamamori,Takagi K,Nakajima N.: "Glucose oxidation in critically ill patients measured with stable isotope and indirect calorimetry" Chiba Med J.74. 393-399 (1998)

1998 年度実績報告書

山森秀夫千葉大学, 医学部, 講師 (00166836)