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Molecular analysis of 4NQO-induced rat tongue cancers using cDNA microarrays - for a purpose of clinical application

Research Project

Project/Area Number 12470399
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 病態科学系歯学(含放射線系歯学)
Research InstitutionKagoshima University

Principal Investigator

SEMBA Ichiro  Kagoshima University, Dental School, Associate Professor, 歯学部, 助教授 (60145505)

Co-Investigator(Kenkyū-buntansha) TANUMA Jun-ichi  Kagoshima University, Dental School, Research Associate, 歯学部, 助手 (20305139)
HIRAYAMA Yoshikazu  Kagoshima University, Dental School, Research Associate, 歯学部, 助手 (50343364)
KITANO Motoo  Kagoshima University, Dental School, Professor, 歯学部, 教授 (10142118)
五味 暁憲  鹿児島大学, 歯学部, 助手 (10325798)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2002: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2001: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2000: ¥6,100,000 (Direct Cost: ¥6,100,000)
Keywords4NQO-induced rat tongue cancer / Experimental model of tongue cancer / Tongue cancer susceptibility gen / cDNA microarray / Signal analysis / Global gene expression / Ratio of the signals of cancer to normal / NQO1-gene / 舌癌抵抗性遺伝子 / コンジェニックラット / 主要組織適合抗原遺伝子 / DNAチップ
Research Abstract

Here we report that use of cDNA microarrays to measure global patterns of gene expression in 4-nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinoma tissue. Measurements of gene expression have been the basis for molecular differentiation of two strains of the rats, highly susceptible Dark-Agouti (DA) rat and poorly susceptible Wistar/Furth (WF) rat (Kitano et al, Jpn J Cancer Res 83, 845-50, 1992 ; Kitano et al, Jpn J Cancer Res 87, 1097-101, 1996). For quantification of the gene expression, fluorescence derived from microarrays hybridized in parallel to control (Cy3-labelled) and 4-nitroquinoline 1-oxide-induced rat tongue cancer (Cy5-labelled) cDNA samples of the two strains of rats were overlayed and analyzed. The expression factor --- evaluated from quadruplicate hybridization --- was determined as a mean value according to the ratios of the Cy5/Cy3 signal intensities. More than 3-fold increases or decreases of the gene expression ratios were regarded as relevant in this experiment. The genes which were up-regulated and down-regulated in a 4NQO-induced tongue cancer (15mm in the diameter) of a DA rat was 337 and 220, respectively, and another 4NQO-induced tongue cancer (5mm in the diameter) developed in a WF rat was 182 and 81, respectively. Regarding the genes previously described as the candidates for QTLs involved in susceptibility of tongue carcinogenesis in the rat (Tanuma et al, Cancer Res 58, 1660-4, 1998 ; Tanuma et al, Jpn J Cancer Res 92, 610-6, 2001 ; Tanuma et al, Int J Cancer 102, 638-42, 2002), microarray analysis demonstrated that the tongue cancers showed a distinct difference in gene expression ratios, for example of NQO1 gene, between the DA rat and WF rat.
These results indicate that the DA rat and WF rat possibly show a distinct signature of differential gene expression in their tongue cancers of which histologic types are the same, I.e., squamous cell carcinoma.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report

Research Products

(37 results)

All Other

All Publications (37 results)

  • [Publications] Tanuma J, Hiai H, Shisa H, Hirano M, Semba I, Nagaoka S, Kitano M: "Carcinogenesis modifier loci in rat tongue are subject to frequent loss of heterozygosity"Int J Cancer. 102. 638-642 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kitano M, Hirano M, Ishihara T, Yoshida A, Hattori S, et al.: "Skeletal muscle necrosis in rat induced by Trimeresurus flavoviridis venom can be prevented by its serum proteins"South Pacific Study. 23. 11-18 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kakimoto K, Machigashira M, Ohnishi T, Kajihara T, Semba I, et al.: "Hepatocyte growth factor in gingival crevicular fluied and the distribution of hepatocyte growth factor-activator in gingival tissue from adult gingivitis"Arch Oral Biol. 47. 655-663 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirano M: "Polymorphism of NQO1(C609T) in relation to susceptibility to oral squmaous cell carcinoma"Oral Med Pathol. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 北野元生, 平野真人, 石原尚, 梅村恵理, 吉田愛知: "ラットにおけるハブ毒による組織障害の特徴(筋肉壊死後の筋肉再生と出血のメカニズムについての考察)"鹿児島大学全学合同プロジェクト離島の豊かな発展のための学際的研究-離島学の構築(No.2)-. (No.2). 97-102 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 仙波伊知郎: "破骨細胞と関連病変"鹿児島大学歯学部紀要. 22. 25-32 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirano M.: "Polymorphism of NQO1(C609T) in relation to susceptibility to oral squamous cell carcinoma."Oral Med Pathol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tanuma J, Hiai H, Shisa H, Hirano M, Semba I, Nagaoka S, Kitano M: "Carcinogenesis modifier loci in rat tongue are subject to frequent loss of heterozygosity."Int J Cancer. 102. 638-642 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kitano M, Hirano M, Ishihara T, Yoshida A, Hattori S, et al.: "Skeletal muscle necrosis in rat induced by Trimeresurus flavoviridis venom can be prevented by its serum proteins."South Pacific Study. 23. 11-18 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kakimoto K, Machigashira M, Ohnishi T, Kajihara T, Semba I, et al.: "Hepatocyte growth factor in gingival crevicular fluid and the distribution of hepatocyte growth factor-activator in gingival tissue from adult gingivitis."Arch Oral Biol. 47. 655-663 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kitano M, Hirano M, Ishihara T, Umemura E, Yoshida A: "Pathomorphogenesis of the skeletal muscle injury in rat induced by Trimeresurus flavoviridis venom."Kagoshima University Project Study; Establishment of island studies. 2. 97-102 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tanuma J, Fujii K, Hirano M, Matsuuchi H, Shisa H, Hiai H, Kitano M: "Five quantitative trait loci affecting 4-nitroquinoline 1-oxide-induced tongue cancer in the rat."Jpn J Cancer Res. 92. 610-616 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watanabe N, Okochi E, Hirayama Y, Shimada Y, Yanagihara K, Yoshida MC, Takahashi S, Mochizuki M, Sugimura T, Nagao M, Ushijima T: "Single nucleotide instability without microsatellite instability in rat mammary carcinomas."Cancer Res. 61. 2632-2640 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kambara K, Sato S, Tanuma J, Tamamura H, Gotoh K, Yoshimori M, Kanamoto T, Kitano M, Nakashima H: "Biological and genetic characterization of a human immunodeficiency virus strain resistant to CXCR4 antagonist T134."AIDS Res Hum Retrov. 17. 615-622 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Landini G, Hirayama Y, Li T-J, Kitano M: "Increased fractal complexity of the epithelial-connective tissue interface in the tongue of 4NQO-treated rats."Pathol Res Pract. 196. 251-258 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tanuma J, Kitano M, Shisa H, Hiai H: "Polygenetic susceptibility and resistance to 4-nitroquinoline 1-oxide-induced tongue carcinoma in the rat."J Exp Anim Sci. 41. 68-77 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Semba I, Nonaka K, Takahashi I, Takahashi K, Dashner R, Shum L, Nuckolls GH, Slavkin HC: "Positionally-dependent chondrogensis induced by BMP4 is conregulated by Sox9 and Msx2."Developm Dynam. 217. 401-414 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tanuma J, Hiai H, Shisa H, Hirano M, Semba I, Nagaoka S, Kitano M.: "Carcinogenesis modifier loci in rat tongue are subject to frequent loss of heterozygosity"Int J Cancer. 102. 638-642 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kitano M, Hirano M, Ishihara T, Yoshida A, Hattori S, et al.: "Skeletal muscle necrosis in rat induced by Trimeresurus flavoviridis venom can be prevented by its serum proteins."South Pacific Study. 23. 11-18 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kakimoto K, Machigashira M, Ohnishi T, Kajihara T, Semba I, et al.: "Hepatocyte growth factor in gingival crevicular fluied and the distribution of hepatocyte growth factor-activator in gingival tissue from adult gingivitis"Arch Oral Biol. 47. 655-663 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hirano M: "Polymorphism of NQO1(C609T) in relation to susceptibility to oral squmaous cell carcinoma"Oral Med Pathol. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] 北野元生, 平野真人, 石原尚, 梅村恵理, 吉田愛知: "ラットにおけるハブ毒による組織傷害の特徴(筋肉壊死後の筋肉再生と出血のメカニズムについての考察)"鹿児島大学全学合同プロジェクト離島の豊かな発展のための学際的研究-離島学の構築(No.2)-. No.2. 97-102 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 仙波伊知郎: "破骨細胞と関連病変"鹿児島大学歯学部紀要. 22. 25-32 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Semba I, Funakoshi K, Kitano M: "Histomorphometric analysis of age changes in the human inferior alveolar artery"Arch Oral Biol. 46. 13-21 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kanbara k, Tanuma J, Gotoh K, Kitano M, Nakashima H, et al.: "Biological and genetic characterization of a human immunodeficiency virus strain resistant to CXCR4 antagonist T134"AIDS Res Human Restrovir. 17. 615-622 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tanuma J, Fujii K, Shisa H, Hiai H, Kitano M, et al.: "Five quantitative trait loci affecting 4-nitroquinoline 1-oxide-induced tongue cancer in the rat"Jpn J Cancer Res. 92. 610-616 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kitano M, Taya Y, Mohri M, Kawashima M: "Dysbaric osteonecrosis(DON)in the femur of an experimental dog : pathological aspects"Kagoshima Univ Res Cnt Pacific Islands, Occasional Papers No.34. 34. 177-183 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Watanabe N, Okochi E, Hirayama Y, Ushijima T, et al.: "Single nucleotide instability without microsatellite instability in rat mammary carcinomas"Cancer Res. 61. 2632-2640 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hirano M, Tanuma J, Tsuneyoshi M, Kitano M, et al.: "Solitary fibrous tumor in the mental region"Pathol Intern. 51. 905-908 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yasui K, Saiga H, Wang Y, Zhang PJ, Semba I: "Early expressed genes showing a dichotomous developing pattern in the lancelet embryo"Dev Growth Differ. 43. 185-194 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kitano M, Hirano M, Ohno M, Hattori S, et al.: "Muscle necrosis and regeneration with lack of marked hemorrhage induced induced in the rat after envenomation of Trimeresurus flavovirides venom and its components phospholipase A2 isozymes"South Pacific Study. 22. 31-39 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kobayashi S,Semba I,Shum L,Slavkin HC,Kulkarnti AB, et al: "Expression pattern of macrophage migration inhibitory factor during embryogenesis"Mech Develop. 84(2). 153-156 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tantuma J,Kitano M,Shisa H,Hiai H.: "Polygenetic susceptibility and resistance to 4-nitroquinoline 1-oxide-induced tongue carcinomas in the rat"J Exp Animal Sci. 41(1). 68-77 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kitano M,Tanuma J,Hirayama Y,Li T-J,Hirano M,Tomita I,Semba I.: "Green tea and rat tongue carcinogenesis (2): mutation of p53 gene during 4NQO-induced carcinogenesis in the Dark-Agouti rat"Reports of Kagoshima University Project : Interactive Studies on Food, Health and Environmental Sciences in Kagoshima . No.3. 137-141 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kitano M.: "Host genes controlling the susceptibility and resistance to squamous cell carcinoma in a rat model"Pathol Intern. 50(5). 353-362 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Landini G,Hirayama Y,Li T-J,Kitano M.: "Increased fractal complexity of the epithelial-connective tissue interface in the tongue of 4NQO-treated rats"Pathol Res Pract. 196(4). 251-258 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Semba I,Ishigami T,Sugihara K,Kitano M: "Higher osteoclastic demineralization and highly mineralized cement lines with osteocalcin deposition in a mandibular cortical bone of autosomal dominant osteoptrosis type II : ultrastructural and undecalcified histological investigations"Bone. 27(3). 389-395 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-03-31   Modified: 2016-04-21  

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