1997 Fiscal Year Annual Research Report

発がんの化学予防

Research Project

Project/Area Number	09253104
Research Category	Grant-in-Aid for Scientific Research on Priority Areas
Research Institution	Kyoto Prefectural University of Medicine
Principal Investigator	西野輔翼京都府立医科大学, 医学部, 教授 (10079709)
Co-Investigator(Kenkyū-buntansha)	朝元誠人国立がんセンター, 化学療法部, 室長 (50212494) 長沢弘明治大学, 農学部, 教授 (10076987) 山本智理子〔財〕癌研究会, 癌研究所・病理部, 研究員 (10280629) 大東肇京都大学, 大学院・農学研究科, 教授 (80026583) 奥山徹明治薬科大学, 薬学部, 教授 (40087789)
Research Abstract	ヒトにおける発がんの化学予防を実用化するために必要な基礎的データを得ることを目的として、多角的な検討を行い、以下の点を明らかにした。 1.発がん抑制に有用な候補化合物として、グリチルレチン酸モノグルクロナイド、タイ国産野菜成分(例えばAL-1など)、イソリクイリチゲニン、シクオキシゲナーゼタイプ2(COX2)の阻害剤(NS-398、ニメスリドなど)、リコピン、ヒドロキシアパタイト、クロロフィリン-キトサンなどを見い出した。 2.ヒト正常型c-Ha-ras遺伝子トランスジェニックラットを用いて、カンキツ類に含まれているd-リモネンの評価を行った。その結果、乳腺発がんを抑制する効果があることを確認できたがその一方で食道発がんを促進する可能性を示唆する結果が得られた。 3.多くの臓器における発がんを抑制する(-)-エピガロカテキンガレートが細胞周期のG2/M期において増殖停止を誘導することが明らかとなった。 4.大腸発がんの抑制効果があることが示唆されているブチレートがWAF-1遺伝子の発現を促進し、細胞周期のG1期において増殖停止を誘導することが明らかとなった。 5.発がつ抑制の研究を進める場合、全く逆からのアプローチも重要である。すなわち、発がん機序を解析することを通して、発がん抑制のための新戦略を考えるということも重要であろう。このような視点に立って、本研究班ではNOが発がんに関与することを今回世界で初めて実験的に証明することに成功した。この結果は、NO系をターゲットにした発がん予防方法を探索することが新しい戦略として考え得ることを示唆している。

Research Products

(47 results)

All Other

All Publications (47 results)

[Publications] Hayatsu,H.: "Inhibitory effects of food-coloring agents derived from Monascus on the mutagenicity of heterocyclic amines." J.Agric.Food Chem.45. 3980-3984 (1997)
[Publications] Ohigashi,H.: "Auraptene,a citrus coumarin,inhibits 12-0-teradecanoylphorbol-13-acetate-inducedtumor promotion in JCR mouse skin,possibly through suppression of superoxide generation in leukocytes" Jpn.J.Cancer Res.88. 443-452 (1997)
[Publications] Ohigashi,H.: "A xanthin oxidase inhibitor 1'-acetoxychavicol acetate inhibits azoxymethane-induced colonic aberrant crypt foci in rats." Carcinogenesis.18. 1113-1118 (1997)
[Publications] Ohigashi,H.: "Chemoprevention of Azoxymethane-induced rat colon carcinogenesis by a xanthin oxidase inhibitor,1'-acetoxychavicol acetate." Jpn.J.Cancer Res.88. 821-830 (1997)
[Publications] Ohigashi,H.: "Citrus auraptene inhibits chemically induced colonic aberrant crypt foci in male F344 rats." Carcinogenesis. 18. 2155-2161 (1997)
[Publications] Asamoto,M.: "Triazine derivatives inhibit rat hepatocarcinogenesis but do not enhance gap junctional intercellular communication." Jpn.J.Cancer Res.88. 12-17 (1997)
[Publications] Asamoto,M.: "Inhibitory Effects of docosahexaenoic acid on colon carcinoma 26 metastasis to the lung." British J.Cancer.75. 650-655 (1997)
[Publications] Asamoto,M.: "Differencial dose-dependent effects of a-,β-carotenes and lycopene on gap junction intercellular communicationin rat liver in vivo." Jpn.J.Cancer Res.88. 1121-1124 (1997)
[Publications] Asamoto,M.: "Inhibitory effects of oleic and docosahexaenoic metalloproteinase-2 and -9 activities." Int.J.Cancer. 73. 607-612 (1997)
[Publications] Asamoto,M.: "Inhibition of azoxymethane-initiated colon tumor by bovine lactferrin administration in F344rats." Jpn.J.Cancer Res.88. 523-526 (1997)
[Publications] Asamoto,M.: "Chemoprevention by lycopene of mouse lung neoplasia after initiation treatment with DEN,MNU and DMH." Cancer Lett.120. 15-22 (1997)
[Publications] Mori,H.: "The Inhibitory Effects of NS-398,a Selective Cyclooxygenase-2 Inhibitor,on Azoxymethane-induced Aberrant Crypt Foci in Colon Carcinogenesis of F344 Rats." Jpn.J.Cancer Res.88. 1044-1051 (1997)
[Publications] Dendaa,A.: "Inhibition by piroxicam of oxidative DNA damage,liver cirrhosis and development of enzyme-altered nodules caused by a cholilne-deficient,L-amino acid-defined diet in rats." Carcinogenesis. 18. 1921-1930 (1997)
[Publications] Denda,A.: "Chemopreventive Efficacy of piroxicam administered alone or in combination with lycopene and b-carotene on the development of rat urinary bladder carcinoma after N-butyl-N-(4-hydroxybutyl)nitrosamine treatment." Jpn.J Cancer Res.88. 543-552 (1997)
[Publications] Denda,A.: "Inhibitory effects of tomato juice on rat urinary bladder carcinogenesis after N-butyl-N-(4-hydroxybutyl)nitrosamine initiation." Jpn.J Cancer Res.89. 22-26 (1998)
[Publications] Nagasawa,H.: "Inhibition by Guan-mu-tong (Caulis aristolochiae manshuriensis) of the growth of spontaneous mammary tumors in SHN virgin mice." Anti-Cancer Drugs. 5. 641-644 (1994)
[Publications] Nagasawa,H.: "Protection by coffee cherry against spontaneous mammary tumour development in mice." Anticancer Res.15. 141-146 (1995)
[Publications] Nagasawa,H.: "Effects of lycopene on spontaneous mammary tumour development in SHN virgin mice" Anticancer Res.15. 1173-1178 (1995)
[Publications] Nagasawa,H.: "Suppression by the growth of spontaneous mammary tumour in SHN mice." Anticancer Res.16. 151-154 (1996)
[Publications] Nagasawa,H.: "Eeffects of lycopene,a carotenoid,on intrathymic T cell differentiation and peripheral CD4/CD8 ratio in a high mammary tumor strain of SHN retired mice." Anti-Cancer Drugs. 75. 195-198 (1996)
[Publications] Nagasawa,H.: "Further study on the effects of coffee cherry on spontaneous mammary tumourigenesis in mice : Effects of methanol extract." Anticancer Res.16. 3507-3514 (1996)
[Publications] Nagasawa,H.: "Effects of aristoloside,a component of guan-mu-tong (Caulis aristolochiae manshuriensis),on normal and preneoplastic mammary gland growth in mice." Anticancer Res.17. 237-240 (1997)
[Publications] Nagasawa,H.: "Effects of Guan-mu-tong (Caulis aristolochiae manshuriensis) in combination with other natural products on normal and preneoplastic mammary gland growth in mice." Amer J Chinese Med.25. 79-88 (1997)
[Publications] Nagasawa,H.: "Inhibition by guadino compounds of growth of spontaneous mammary tumours in SHN mice." Anticancer Res.17. 3349-3354 (1997)
[Publications] Sakai,T.: "Hypermethylation in the retinoblastoma gene is associated with unilateral,sporadic retinoblastoma." Cancer Genetics and Cytogenetics. 98. 43-49 (1997)
[Publications] Sakai,T: "Effects of Quercetin and/or restraint stress on formation of aberrant crypt foci induced by azoxymethane in rat colons." Oncology. 54. 118-121 (1997)
[Publications] Sakai,T: "Bytyrate activates the WAF1/Cip1 gene promoter through Sp1 sites in a p53-negative human colon cancer cell line." J.Biol.Chem.272. 22199-22206 (1997)
[Publications] Sakai,T: "Molecular cloning and characterization of the human p27Kip1 gene promoter." FEBS Lett.411. 1-6 (1997)
[Publications] Sakai,T: "Retinoblastoma binding factor 1 site in the core promoter region of the human RB gene is activated by hGABP/E4TF1." Cancer Res.57. 3145-3148 (1997)
[Publications] Sakai,T: "Ammonia inhibits proliferation and cell cycle progression at S-phase in human gastric cells." Dig.Dis.Sci.42. 1394-1399 (1997)
[Publications] Sakai,T.: "Histone deacetylase inhibitor activates the WAF1/Cip1 gene promoter through the Sp1 sites." Biochem.Biophys.Res.Commun.241. 142-150 (1997)
[Publications] Fujiki,H.: "Tumor promotion and TNF-a gene expression by the okadaic acid class tumor promoters" Envir.Carcino.& Ecotox Revs.15. 1-40 (1997)
[Publications] Fujiki,H.: "Mechanisms of growth inhibition of human lung cancer cell line,PC-9,by tea polyphenols" Jpn.J.Cancer Res.88. 639-643 (1997)
[Publications] Fujiki,H.: "Expression of the tumor necrosis factor a gene and early response genes by nodularin,a liver tumor promoter,in primary cultured rat hepatocytes." J.Cancer Res.Clin.Oncol.123. 413-419 (1997)
[Publications] Fujiki,H.: "Sealing effects of (-)-epigalocatedchin gallate on protein kinase C and protein phosphatase 2A." Biophys.Chem.65. 157-164 (1997)
[Publications] Okuyama,T.: "Studies of the constituents of astragalus membraceus bunge. III.Structures of triterpenoidal glucosides,huangqiyenins A and B,from the leaves." Chem.Pharm.Bull.45. 359-361 (1997)
[Publications] Okuyama,T.: "Studies on cancer chamoprevention by traditional folk medicines. XV,antitumor-promoting effect of white pepper,piper nigrum and piperine in vitro and in vivo carcinogenesis." J.Tranditional Medicines. 14. 89-95 (1997)
[Publications] Nishino,H.: "Inhibitory effects on Epstein-Barr virus activation of anthraquinones : Correlation with redox potentials" Cancer Lett.115. 179-183 (1997)
[Publications] Nishino,H.: "Chemoprevention by lycopene of mouse lung neoplasia after combined inhibition treatment with DEN,MNU and DMH." Cancer Lett.120. 15-22 (1997)
[Publications] Nishino,H.: "Differential dose-dependent effects of α-,β-carotenes and lycopene on gap-junctional intercellular communication in rat liver in vivo." Jpn.J.Cancer Res.88. 1121-1124 (1997)
[Publications] Nishino,H.: "Inhibitory effect of soybean hypocotyls on Epstein-Barr virus early antigen induction and ski tumor promotion." Cancer Lett.121. 53-57 (1997)
[Publications] Nishino,H.: "Inhibitory effects of quassinoid derivatives on Epstein-Barr virus early antigen activation." Chem.Pharm.Bull.45. 675-677 (1997)
[Publications] Nishino,H.: "Anti-tumor promoting activities of isoflavonoids from Wistaria brachybotrys." Biol.Pharm.Bull.20. 865-868 (1997)
[Publications] Fujiki,H.: "Food Factors for Cancer Prevention" H.Ohigashi, T.Osawa, J.Terao, S.Watanabe, and T.Yoshikawa, 127-129 (1997)
[Publications] Fujiki,H.: "Comprehensive Toxicology vol.12" G.T.Bowden and S.M.Fischer, 453-471 (1997)
[Publications] Fujiki,H.: "Clinical and Biological Basis of Lung Cancer Prevention." Martinet,Y., Hirsch,F.R., Martinet,N., Vignaud,J.-M., Mulshine,J.L., 285-290 (1997)
[Publications] Nishino,H.: "Food Factors for Cancer Prevention" H.Ohigashi, T.Osawa, J.Terao, S.Watanabe, and T.Yoshikawa, 529-532, 533-537, 607-612 (1997)

1997 Fiscal Year Annual Research Report

発がんの化学予防

Principal Investigator

西野 輔翼 京都府立医科大学, 医学部, 教授 (10079709)

Research Products

[Publications] Hayatsu,H.: "Inhibitory effects of food-coloring agents derived from Monascus on the mutagenicity of heterocyclic amines." J.Agric.Food Chem.45. 3980-3984 (1997)

[Publications] Ohigashi,H.: "Auraptene,a citrus coumarin,inhibits 12-0-teradecanoylphorbol-13-acetate-inducedtumor promotion in JCR mouse skin,possibly through suppression of superoxide generation in leukocytes" Jpn.J.Cancer Res.88. 443-452 (1997)

[Publications] Ohigashi,H.: "A xanthin oxidase inhibitor 1'-acetoxychavicol acetate inhibits azoxymethane-induced colonic aberrant crypt foci in rats." Carcinogenesis.18. 1113-1118 (1997)

[Publications] Ohigashi,H.: "Chemoprevention of Azoxymethane-induced rat colon carcinogenesis by a xanthin oxidase inhibitor,1'-acetoxychavicol acetate." Jpn.J.Cancer Res.88. 821-830 (1997)

[Publications] Ohigashi,H.: "Citrus auraptene inhibits chemically induced colonic aberrant crypt foci in male F344 rats." Carcinogenesis. 18. 2155-2161 (1997)

[Publications] Asamoto,M.: "Triazine derivatives inhibit rat hepatocarcinogenesis but do not enhance gap junctional intercellular communication." Jpn.J.Cancer Res.88. 12-17 (1997)

[Publications] Asamoto,M.: "Inhibitory Effects of docosahexaenoic acid on colon carcinoma 26 metastasis to the lung." British J.Cancer.75. 650-655 (1997)

[Publications] Asamoto,M.: "Differencial dose-dependent effects of a-,β-carotenes and lycopene on gap junction intercellular communicationin rat liver in vivo." Jpn.J.Cancer Res.88. 1121-1124 (1997)

[Publications] Asamoto,M.: "Inhibitory effects of oleic and docosahexaenoic metalloproteinase-2 and -9 activities." Int.J.Cancer. 73. 607-612 (1997)

[Publications] Asamoto,M.: "Inhibition of azoxymethane-initiated colon tumor by bovine lactferrin administration in F344rats." Jpn.J.Cancer Res.88. 523-526 (1997)

[Publications] Asamoto,M.: "Chemoprevention by lycopene of mouse lung neoplasia after initiation treatment with DEN,MNU and DMH." Cancer Lett.120. 15-22 (1997)

[Publications] Mori,H.: "The Inhibitory Effects of NS-398,a Selective Cyclooxygenase-2 Inhibitor,on Azoxymethane-induced Aberrant Crypt Foci in Colon Carcinogenesis of F344 Rats." Jpn.J.Cancer Res.88. 1044-1051 (1997)

[Publications] Dendaa,A.: "Inhibition by piroxicam of oxidative DNA damage,liver cirrhosis and development of enzyme-altered nodules caused by a cholilne-deficient,L-amino acid-defined diet in rats." Carcinogenesis. 18. 1921-1930 (1997)

[Publications] Denda,A.: "Chemopreventive Efficacy of piroxicam administered alone or in combination with lycopene and b-carotene on the development of rat urinary bladder carcinoma after N-butyl-N-(4-hydroxybutyl)nitrosamine treatment." Jpn.J Cancer Res.88. 543-552 (1997)

[Publications] Denda,A.: "Inhibitory effects of tomato juice on rat urinary bladder carcinogenesis after N-butyl-N-(4-hydroxybutyl)nitrosamine initiation." Jpn.J Cancer Res.89. 22-26 (1998)

[Publications] Nagasawa,H.: "Inhibition by Guan-mu-tong (Caulis aristolochiae manshuriensis) of the growth of spontaneous mammary tumors in SHN virgin mice." Anti-Cancer Drugs. 5. 641-644 (1994)

[Publications] Nagasawa,H.: "Protection by coffee cherry against spontaneous mammary tumour development in mice." Anticancer Res.15. 141-146 (1995)

[Publications] Nagasawa,H.: "Effects of lycopene on spontaneous mammary tumour development in SHN virgin mice" Anticancer Res.15. 1173-1178 (1995)

[Publications] Nagasawa,H.: "Suppression by the growth of spontaneous mammary tumour in SHN mice." Anticancer Res.16. 151-154 (1996)

[Publications] Nagasawa,H.: "Eeffects of lycopene,a carotenoid,on intrathymic T cell differentiation and peripheral CD4/CD8 ratio in a high mammary tumor strain of SHN retired mice." Anti-Cancer Drugs. 75. 195-198 (1996)

[Publications] Nagasawa,H.: "Further study on the effects of coffee cherry on spontaneous mammary tumourigenesis in mice : Effects of methanol extract." Anticancer Res.16. 3507-3514 (1996)

[Publications] Nagasawa,H.: "Effects of aristoloside,a component of guan-mu-tong (Caulis aristolochiae manshuriensis),on normal and preneoplastic mammary gland growth in mice." Anticancer Res.17. 237-240 (1997)

[Publications] Nagasawa,H.: "Effects of Guan-mu-tong (Caulis aristolochiae manshuriensis) in combination with other natural products on normal and preneoplastic mammary gland growth in mice." Amer J Chinese Med.25. 79-88 (1997)

[Publications] Nagasawa,H.: "Inhibition by guadino compounds of growth of spontaneous mammary tumours in SHN mice." Anticancer Res.17. 3349-3354 (1997)

[Publications] Sakai,T.: "Hypermethylation in the retinoblastoma gene is associated with unilateral,sporadic retinoblastoma." Cancer Genetics and Cytogenetics. 98. 43-49 (1997)

[Publications] Sakai,T: "Effects of Quercetin and/or restraint stress on formation of aberrant crypt foci induced by azoxymethane in rat colons." Oncology. 54. 118-121 (1997)

[Publications] Sakai,T: "Bytyrate activates the WAF1/Cip1 gene promoter through Sp1 sites in a p53-negative human colon cancer cell line." J.Biol.Chem.272. 22199-22206 (1997)

[Publications] Sakai,T: "Molecular cloning and characterization of the human p27Kip1 gene promoter." FEBS Lett.411. 1-6 (1997)

[Publications] Sakai,T: "Retinoblastoma binding factor 1 site in the core promoter region of the human RB gene is activated by hGABP/E4TF1." Cancer Res.57. 3145-3148 (1997)

[Publications] Sakai,T: "Ammonia inhibits proliferation and cell cycle progression at S-phase in human gastric cells." Dig.Dis.Sci.42. 1394-1399 (1997)

[Publications] Sakai,T.: "Histone deacetylase inhibitor activates the WAF1/Cip1 gene promoter through the Sp1 sites." Biochem.Biophys.Res.Commun.241. 142-150 (1997)

[Publications] Fujiki,H.: "Tumor promotion and TNF-a gene expression by the okadaic acid class tumor promoters" Envir.Carcino.& Ecotox Revs.15. 1-40 (1997)

[Publications] Fujiki,H.: "Mechanisms of growth inhibition of human lung cancer cell line,PC-9,by tea polyphenols" Jpn.J.Cancer Res.88. 639-643 (1997)

[Publications] Fujiki,H.: "Expression of the tumor necrosis factor a gene and early response genes by nodularin,a liver tumor promoter,in primary cultured rat hepatocytes." J.Cancer Res.Clin.Oncol.123. 413-419 (1997)

[Publications] Fujiki,H.: "Sealing effects of (-)-epigalocatedchin gallate on protein kinase C and protein phosphatase 2A." Biophys.Chem.65. 157-164 (1997)

[Publications] Okuyama,T.: "Studies of the constituents of astragalus membraceus bunge. III.Structures of triterpenoidal glucosides,huangqiyenins A and B,from the leaves." Chem.Pharm.Bull.45. 359-361 (1997)

[Publications] Okuyama,T.: "Studies on cancer chamoprevention by traditional folk medicines. XV,antitumor-promoting effect of white pepper,piper nigrum and piperine in vitro and in vivo carcinogenesis." J.Tranditional Medicines. 14. 89-95 (1997)

[Publications] Nishino,H.: "Inhibitory effects on Epstein-Barr virus activation of anthraquinones : Correlation with redox potentials" Cancer Lett.115. 179-183 (1997)

[Publications] Nishino,H.: "Chemoprevention by lycopene of mouse lung neoplasia after combined inhibition treatment with DEN,MNU and DMH." Cancer Lett.120. 15-22 (1997)

[Publications] Nishino,H.: "Differential dose-dependent effects of α-,β-carotenes and lycopene on gap-junctional intercellular communication in rat liver in vivo." Jpn.J.Cancer Res.88. 1121-1124 (1997)

[Publications] Nishino,H.: "Inhibitory effect of soybean hypocotyls on Epstein-Barr virus early antigen induction and ski tumor promotion." Cancer Lett.121. 53-57 (1997)

[Publications] Nishino,H.: "Inhibitory effects of quassinoid derivatives on Epstein-Barr virus early antigen activation." Chem.Pharm.Bull.45. 675-677 (1997)

[Publications] Nishino,H.: "Anti-tumor promoting activities of isoflavonoids from Wistaria brachybotrys." Biol.Pharm.Bull.20. 865-868 (1997)

[Publications] Fujiki,H.: "Food Factors for Cancer Prevention" H.Ohigashi, T.Osawa, J.Terao, S.Watanabe, and T.Yoshikawa, 127-129 (1997)

[Publications] Fujiki,H.: "Comprehensive Toxicology vol.12" G.T.Bowden and S.M.Fischer, 453-471 (1997)

[Publications] Fujiki,H.: "Clinical and Biological Basis of Lung Cancer Prevention." Martinet,Y., Hirsch,F.R., Martinet,N., Vignaud,J.-M., Mulshine,J.L., 285-290 (1997)

[Publications] Nishino,H.: "Food Factors for Cancer Prevention" H.Ohigashi, T.Osawa, J.Terao, S.Watanabe, and T.Yoshikawa, 529-532, 533-537, 607-612 (1997)

西野輔翼京都府立医科大学, 医学部, 教授 (10079709)