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Study on Molecular Analysis and Chemoprevention of Oral Carcinogenesis Using a Rat Oral Carcinogenesis Model

Research Project

Project/Area Number 05671568
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 病態科学系歯学(含放射線系歯学)
Research InstitutionGifu University School of Medicine

Principal Investigator

TANAKA Takuji  Gifu Univ.Sch.Med., Pathology, Associate Professor, 医学部, 助教授 (40126743)

Co-Investigator(Kenkyū-buntansha) MORI Hideki  Gifu Univ.Sch.Med., Pathology, Professor, 医学部, 教授 (70021433)
YOSHIMI Naoki  Gifu Univ.Sch.Med., Pathology, Instructor, 医学部, 講師 (30166996)
SUGIE Shigeyuki  Gifu Univ.Sch.Med., Animal Fac., Associate Professor, 医学部附属動物実験施設, 助教授 (60187648)
Project Period (FY) 1993 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1995: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1993: ¥900,000 (Direct Cost: ¥900,000)
KeywordsMolecular analysis / Phenotypic alteration / Cancer chemoprevention / 4-Nitroquinoline 1-oxide / Oral carcinogenesis / Progression / Rat / プロトカテク酸 / 化学予防 / ラット / 4-nitroquinoline l-oxide / フラボノイド / レチノイド / 遺伝子変異 / K-ras / Protocatechuic acid / GGT / GST-P / p53 / ki-ras
Research Abstract

To clarify carcinogenesis process of oral cancer and to prevent this cancer, molecular analysis and search of chemopreventive agents against oral carcinogenesis were done using a 4-nitroquinoline 1-oxide (4-NQO)-induced rat oral carcinogenesis model. The results obtained were as follows : 1.Molecular analysis using PCR-SSCP technique revealed infrequent Ha-ras and absence of Ki-ras, N-ras, and p53 mutations in 4-NQO induced rat oral lesions. 2.Histological studies revealed mutistep nature of 4-NQO-induced oral carcinogenesis and strong expression of GGT and GST-P or weakly positive for c-myc, c-fos, c-Ha-ras, c-erbB,p53 in the lesions. 3.Protocatechuic acid (PCA), hesperidin, curcumin, 1'-acetoxychavicol acetate, beta-carotene, astaxanthin, and canthaxanthin effectively suppressed rat oral carcinogenesis. 4.Indole-3-carbinol could inhibit spontaneous endometrial cancer development as well as oral and liver cell neoplasms. 5.PCA,astaxanthin, and canthaxanthin could also inhibit other organs' tumorigenesis (colon, liver, stomach, and bladder) in rats. 6.KYN-54 and mofarotene prevented rat oral carcinogenesis. 7.PCA had anti-progression effects on rat oral carcinogenesis. 8.These results may indicate that all tested compounds are possible chemopreventive agents against oral cancer. Although inhibition in cell proliferation activity in the oral mucosa might be suspected, further studies on the precise mechanisms of inhibition should be done.

Report

(4 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (59 results)

All Other

All Publications (59 results)

  • [Publications] Takuji Tanaka,et al.: "Chemoprevention of mouse urinary bladder carcinogenesis by the naturally occurring carotenoid astaxanthin" Carcinogenesis. 15. 15-19 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Toshihiro Kojima,Takuji Tanaka,et al.: "Chemoprevention of spontaneous endometrial cancer in female Donryu rats by dietary indole-3-carbinol" Cancer Research. 54. 1446-1449 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takuji Tanaka,et al.: "Chemoprevention of 4-nitroquinoline 1-oxide-induced oral carcinogenesis by dietary protocatechuic acid during initiation and postinitiation phases" Cancer Research. 54. 2359-2365 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takuji Tanaka,et al.: "Chemoprevention of 4-nitroquinoline 1-oxide-induced oral carcinogenesis by dietary curcumin and hesperidin : comparison with the protective effect of β-carotene" Cancer Research. 54. 4653-4659 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takuji Tanaka: "Cancer chemoprevention by natural products (Review)" Oncology Reports. 1. 1139-1155 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takuji Tanaka: "Chemoprevention of oral carcinogenesis" Oral Oncology,European Journal of Cancer. 31B. 3-15 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takuji Tanaka,et al.: "Chemoprevention of digestive organs carcinogenesis by natural product protocatechuic acid" Cancer. 75. 1433-1439 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masumi Suzuki,Naoki Yoshimi,Takuji Tanaka,et al.: "Infrequent H-ras mutations and absence of K-ras or p53 mutations in 4-nitroquinoline 1-oxide-induced rat tongue lesions : a multistage oral cancer model for human oral squamous cell carcinomas" Molecular Carcinogenesis. 14. 294-298 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takuji Tanaka,et al.: "Chemoprevention of N-methyl-N-nitrosourea-induced rat glandular stomach carcinogenesis by a natural product protocatechuic acid" Cancer Journal. 8. 150-156 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takuji Tanaka,et al.: "Inhibition of oral carcinogenesis by the arotinoid mofarotene (Ro 40-8757) in male F344 rats" Carcinogenesis. 16. 1903-1907 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hiroki Makita,Takuji Tanaka,et al.: "Inhibition of 4-nitroquinoline 1-oxide-induced rat oral carcinogenesis by dietary exposure of a new retinoidal butenolide,KYN-54,during the initiation and postinitiation phases" Carcinogenesis. 16. 2171-2176 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takuji Tanaka,et al.: "Chemoprevention of rat oral carcinogenesis by naturally occurring xanthophylls astaxanthin and canthaxanthin" Cancer Research. 55. 4059-4064 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takuji Tanaka,et al: "Oral Oncology, Vol.IVB : Fundamental" Macmillan India,Ltd., 380 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takuji Tanaka: "Proceedings of International Conference on Food Factors-Chemistry and Cancer Prevention-" Springer-Verlag,Tokyo, (in press) (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takuji Tanaka, Yukio Morishita, Masumi Suzui, Toshihiro Kojima, Ataru Okumura, and Hideki Mori: "Chemoprevention of mouse urinary bladder carcinogenesis by the naturally occurring carotenoid astaxanthin." Carcinogenesis. 15. 15-19 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Toshihiro Kojima, Takuji Tanaka, and Hideki Mori: "Chemoprevention of spontaneous endometrial cancer in female Donryu rats by dietary indole-3-carbinol." Cancer Res.54. 1446-1449 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takuji Tanaka, Toshihiko Kawamori, Masami Ohnishi, Kiyohisa Okamoto, Hideki Mori, and Akira Hara: "Chemoprevention of 4-nitroquinoline 1-oxide-induced oral carcinogenesis by dietary protocatechuic acid during initiation and post-initiation phases." Cancer Res.54. 2359-2365 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takuji Tanaka, Hiroki Makita, Masami Ohnishi, Yoshinobu Hirose, Aijin Wang, Hideki Mori, Kumiko Satoh, Akira Hara, and Hiroshi Ogawa: "Chemoprevention of 4-nitroquinoline 1-oxide-induced oral carcinogenesis by dietary curcumin and hesperidin : comparison with the protective effect of beta-carotene." Cancer Res.54. 4653-4659 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takuji Tanaka: "Cancer chemoprevention by natural products (Review)." Oncol.Reports. 1. 1139-1155 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takuji Tanaka: "Chemoprevention of oral carcinogenesis." Oral Oncol Eur.J.Cancer. 31B. 3-15 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takuji Tanaka, Toshihiro Kojima, Toshihiko Kawamori, and Hideki Mori: "Chemoprevention of digestive organs carcinogenesis by natural product protocatechuic acid." Cancer. 75. 1433-1439 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masumi Suzui, Naoki Yoshimi, Takuji Tanaka, and Hideki Mori: "Infrequent H-ras mutations and absence of K-ras or p53 mutations in 4-nitroquinoline 1-oxide-induced rat tongue lesions : a multistage oral cancer model for human oral squamous cell carcinomas." Mol.Carcinogenesis. 14. 294-298 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takuji Tanaka, Masami Ohnishi, Toshihiro Kojima, Hideki Mori, Kumiko Satoh, and Akira Hara: "Chemoprevention of N-methyl-N-nitrosourea-induced rat glandular stomach carcinogenesis by a natural product protocatechuic acid." Cancer J.8. 150-156 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takuji Tanaka, Hiroki Makita, Masami Ohnishi, Hideki Mori, Kumiko Satoh, and Akira Hara: "Inhibition of oral carcinogenesis by the arotinoid mofarotene (Ro 40-8757) in male F344 rats." Carcinogenesis. 16. 1903-1907 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hiroki Makita, Takuji Tanaka, Masami Ohnishi, Yoshin Tamai, Masahiro Torihara, Johji Yamahara, Hideki Mori, Kumiko Satoh, and Akira Hara: "Inhibition of 4-nitroquinoline 1-oxide-induced rat oral carcinogenesis by dietary exposure of a new retinoidal butenolide, KYN-54, during the initiation and postinitiation phases." Carcinogenesis. 16. 2171-2176 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takuji Tanaka, Hiroki Makita, Masami Ohnishi, Hideki Mori, Kumiko Satoh, and Akira Hara: "Chemoprevention of rat oral carcinogenesis by naturally occurring xanthophylls astaxanthin and canthaxanthin." Cancer Res.55. 4059-4064 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takuji Tanaka, Toshihiko Kawamori, Masami Ohnishi, Hiroki Makita, Hideki Mori, Kumiko Satoh, and Akira Hara: "Suppression of azoxymethane-induced rat colon carcinogenesis by dietary administration of naturally occurring xanthophylls astaxanthin and canthaxanthin during the post-initiation phase." Carcinogenesis. 16. 2957-2963 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takuji Tanaka, Hiroki Makita, Masami Ohnishi, and Hideki Mori: "Chemoprevention of 4-NQO-induced oral carcinogenesis by xanthophylls (astaxanthin and canthaxanthin) and a xanthine oxidase inhibitor 1'-acetoxychavicol acetate in rats. In : A.K.Varma and M.Mori (eds.), Oral Oncology." Macmillan India, Ltd., New Delhi.Vol.IVB : FUNDAMENTAL. 365-368 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masami Ohnishi, Takuji Tanaka, Hiroki Makita, Toshihiko Kawamori, Hideki Mori, Kumiko Satoh, Akira Hara, Akira Murakami, Hajime Ohigashi, and Koichi Koshimizu: "Chemopreventive effect of a xanthine oxidase inhibitor 1'-acetoxychavicol acetate on rat oral carcinogenesis." Jpn.J.Cancer Res.87 : (in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takuji Tanaka: "Chemoprevention of oral and colon carcinogenesis by natural compounds protocatechuic acid, 1'-acetoxychavicol acetate, S-methyl methane thiosulfonate, and hesperidin from vegetables and fruits. Proceedings of International Conference on Food Factors-Chemistry and Cancer Prevention -" Springer-Verlag, Tokyo. (in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Toshihiro Kojima, Takuji Tanaka, et al.: "Chemoprevention of spontaneous endometrial cancer in female Donryu rats by dietary indole-3-carbinol" Cancer Research. 54. 1446-1449 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takuji Tanaka: "Chemoprevention of oral carcinogenesis" Oral Oncology, Eurpean Journal of Cancer. 31B. 3-15 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takuji Tanaka, et al.: "Chemoprevention of digestive organs carcinogenesis by natural product protocatechuic acid" Cancer. 75. 1433-1439 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Masumi Suzui, Naoki Yoshimi, Takuji Tanaka, et al.: "Infrequent H-ras mutations and absence of K-ras or p53 mutations in 4-nitroauinoline 1-oxide-induced rat tongue lesions: a multistage oral cance model for human oral squamous cell carcinomas" Molecular Carcinogenesis. 14. 294-298 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takuji Tanaka, et al.: "Chemoprevention of N-methyl-N-nitrosourea-induced rat glandular stomach carcinogenesis by natural product protocatechuic acid" Cancer Journal. 8. 150-156 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takuji Tanaka, et al.: "Inhibition of oral carcinogenesis by the arotinoid mofarotene (Ro 40-8757) in male F344 rats" Carcinogenesis. 16. 1903-1907 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hiroki Makita, Takuji Tanaka, et al.: "Inhibition of 4-nitroquinoline 1-oxide-induced rat oral carcinogenesis by dietary exposure of a new retinoidal butenolide,KYN-54, during the initiation and postinitiation phases" Carcinogenesis. 16. 2171-2176 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takuji Tanaka, et al.: "Chemoprevention of rat oral carcinogenesis by naturally occurring xanthophylls astaxanthin and canthaxanthin" Cancer Research. 55. 4059-4064 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takuji Tanaka, et al.: "Suppression of azoxymethane-induced rat colon carcinogenesis by dietary administration of naturally occurring xanthophylls staxanthin and canthaxanthin during the postinitiation phase" Carcinogenesis. 16. 2957-2963 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Masami Ohnishi, Takuji Tanaka, et al.: "Chemopreventive effect of a xanthine oxidase inhibitor 1′-acetoxychavicol acetate on rat oral carcinogenesis" Japaness Journal of Cancer Research. 87(in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takuji Tanaka, et al.: "Oral Oncology, Volume IVB: Fundamental" Varma AK and Mori H, 380 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takuji Tanaka, et al.: "Proceedings of International Conference on Food Factors-Chemistry and Cancer Prevention-" Osawa T, et al. (in press), (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takuji,Tanaka: "Cancer chemoprevention by natural products(Review)" Oncoloqy Reports. 1. 1139-1155 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takuji,Tanaka,et al.: "Chemoprevention of mouse urinary bladder carcinogenesis by the naturally occurring carotenoid astaxanthin" Carcinogenesis. 15. 15-19 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takuji,Tanaka,et al.: "Chemoprevention of 4-nitroquinoline l-oxide-induced oral carcino-genesis by dietary protocatechuic acid during initiation and postinitiation phases" Cancer Research. 54. 2359-2365 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Toshihiko,Kawamori,et al.: "Suppression of azoxymethane-induced rat colon aberrant crypt foci by dietary protocatechuic acid" Japanese Journal of Cancer Research. 85. 686-691 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takuji,Tanaka,et al.: "Chemoprevention of 4-nitroquinoline l-oxide-induced oral carcino-genesis by dietary curcumin and hesperidin:comparison with the protective effect of β-carotene" Cancer Research. 54. 4653-4659 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hideki,Mori,et al.: "Antimutagenesis and Anticarcinogenesis Mechanisms III" Bronzetti G,Hayatsu H,De Flora S,Waters MD,and Shankel DM:Plenum Press, 494 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Tanaka T,Kojima T,Okumura A,Sugie T,Mori H: "Inhibitory effect ofthe non-steroidal anti-inflammatory drugss,indomethacin and piroxicam on2-acetylaminofluorene-induced hepatocarcinogenesis in male ACI/N rats" Cancer Letters. 68. 111-118 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tanaka T,Kojima T,Haraara A,Sawada H,Mori H: "Chemoprevention of oral carcinogenesis by D,L-α-difluoromethylornithine,an ornithine decarboxylase inhibitor:dose dependent reduction in 4-nitroquinoline 1-oxide-induced tongue neoplasms in rats" Cancer Research. 53. 772-776 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tanaka T,Kojima T,Kawamori T,Yoshimi N,Mori H: "Chemoprevention of diethylnitrosamine-induced hepatocarcinogenesis by a simple phenolic acid protocatechuic acid in rats" Cancer Research. 53. 2775-2779 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tanaka T,Kojima T,Suzui M,Mori H: "Chemoprevention of colon carcinogenesis by the natural product of a simple phenolic compound protocatechuic acid:suppressing effects on tumor development and biomarkers expression of colon tumorigenesis" Cancer Research. 53. 3908-3913 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tanaka T,Morishita Y,Kawamori T,Suzui M,Kojima T,Mori H.: "Synergistic effect of radiation on colon carcinogenesis by methylazoxymethanol acetate in ACI/N rats" Japanese Journal of Cancer Research. 1031-1036 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kojima T,Tanaka T,Kawamori T,Suzui M,Hara A,Mori H: "Chemoprevention of dietary D,L-α-difluoromethylornithine,an ornithine decarboxylase inhibitor,on initiation and post-initiation stages of diethylnitrosamine induced rat hepatocarcinogenesis" Cancer Research. 53. 3903-3907 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tanaka T,Morishita Y,Suzui M,Kojima T,Okumura A,Mori H: "Chemoprevention of mouse urinary bladder carcinogenesis by the naturally occurring carotenoid astaxanthin" Carcinogenesis. 15. 15-19 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kojima T,Tanaka T,Mori H: "Chemoprevention of spontaneous endometrial cancer in female Donryu rats by dietary indole-3-carbinol" Cancer Research. 54 (in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Mori H,Tanaka T: "Chemopreventive retinoids" Drugs of the Future. 18. 737-742 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tanaka T: "Chemoprevention of human cancer:Biology and therapy" Critical Review in Oncology/Hematology. (in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Mori H,Morishita Y,Tanaka T: "Preventive effect of magnesium hydroxide on carcinogen-induced large bowel carcinogenesis in rats" Bonzatt G,De Flora S,Shankel DM,Hayatsu H:Plenum Press, 111-118 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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