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Pharmacogenetics of drug metabolizing enzymes

Research Project

Project/Area Number 07672337
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

YOKOI Tsuyoshi  Hokkaido Univ., Fac.of Pharm.Res.Associate Prof., 薬学部, 助教授 (70135226)

Co-Investigator(Kenkyū-buntansha) KAMATAKI Tetsuya  Hokkaido Univ., Fac.of Pharm.Res.Prof., 薬学部, 教授 (00009177)
NAKAYAMA Katsuo  Hokkaido Univ., Fac.of Pharm.Res.Instructor, 薬学部, 助手 (20261323)
藤田 健一  北海道大学, 薬学部, 教務職員 (60281820)
佐久間 勉  北海道大学, 薬学部, 助手 (30250468)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1995: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordsgenotyping / SM-12502 / coumarin / poor metabolizer / polymorphism / CYP2A6 / population study / チトクロームP450 2D6 / チトクロームP450 2A6 / drugmetabolism / 発がん / 代謝的活性化 / CYP2D6 / poor metabolizer / CYP1A2
Research Abstract

Genetic polymorphism of CYP2A6 was investigates. (+) -cis-3,5-dimethyl-2- (3-pyridyl) thiazolidin-4-one hydrochloride (SM-12502) was found to be a specific substrate of CYP2A6. Genomic DNA form extensive metabolizers and poor metabolizers (PM) of SM-12502 were examined by Southern blot analysis with CYP2A6cDNA probe. A new Sac I-RELP which distinguish PM was investigated. Finally, we concluded that the PM of SM-12502 was responsible for CYP2A6 whole gene deletion. A new genotyping method for CYP2A6 whole gene deletion with PCR was developed.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] H. Hashimoto: "Fetus-speclfic CY P3A7 and adult-specific CYP3A4 expressed in Chinese hamster CHL cells have similar capacity to activate carcinogenic mycotoxins." Cancer Research. 55. 787-791 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T. Sakuma: "Is olation on and character izalion of a new cDNA done belonging to the oytochrome P450 2C gene subfamily in hamsters." Archs. Bicchem. Biophys.319. 267-273 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K. Nunoya: "S-oxidation of (+)-αs-3,5-dimethy1-2- (-pyridyl) -thiazoli-din-4-one hydrochioride (SM-12502) by rat hepatic flavin-containing monooxygenase 1 expressed in yeast." Xenobiotica. 25. 1283-1299 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K. Nunoya: "(+)-αs-3,5-dimethyl-2- (3-pyridyl) thiazolin-4-one Hydrochloride (SM-12502) as a novel substrate for cytochrome P450 2A6 (CYP2A6) in human liver microsomes." J. Pharmacol. Expl. Therap.277. 768-774 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T. Yokoi: "A new CYP2D6 allele with a nine base insertion on in ex on 9 in a Japanese population associated with poor metabolizer phenotype." Pharmacogenetics. 6. 395-401 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K. Nakamura: "CYP2D6 is a pricipal cytochrome P450 responsible for metabolism of the histamine H1 antagonist promethazine in human liver microsomes." Pharmacogenetics. 6. 449-457 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hisashi Hashimoto, Tetsuya Nakagawa, Tsuyoshi Yokoi, Minoru Sawada, Susumu Itoh and Tetsuya Kamataki: "Fetus-specific CYP3A7 and adult-specific CYP3A4 expressed in Chinese hamster CHL cells have similar capacity to activate carcinogenic mycotoxins" Cancer Res.55. 787-791 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tsutomu Sakuma, Tsuyoshi Yokoi and Tetsuya Kamataki: "Isolation and characterization of a new cDNA clone belonging to the cytochrome P450 2C gene subfamily in hamsters" Archs.Biochem.Biophys.319. 267-273 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ken-ichi Nunoya, Tsuyoshi Yokoi, Kunio Itoh, Susumu Itoh, Kanzo Kimura and Tetsuya Kamataki: "S-oxidation of (+) -cis-3,5-dimethyl-2- (-pyridyl) -thiazoli-din-4-one hydrochloride (SM-12502) by rat hepatic flavin-containing monooxygenase 1 expressed in yeast" Xenobiotica. 25. 1283-1291 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ken-ichi Nunoya, Tsuyoshi Yokoi, Kanzo Kimura, Takao Kodama, Masahito Funayama, Kazuaki Inoue, Kazuo Nagashima, Yoshihiko Funae, Noriaki Shimada, Carol Green and Tetsuya Kamataki: "(+) -cis-3,5-dimethyl-2- (3-pyridyl) thiazolin-4-one Hydrochloride (SM-12502) as a novel substrate for cytochrome P450 2A6 (CYP2A6) in human liver microsomes" J.Pharmacol.Exptl.Therap.277. 768-774 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tsuyoshi Yokoi, Yasuyuki Kosaka, Michihiro Chiba, Kan Chiba, Hidefumi Nakamura, Takashi Ishizaki, Moritoshi Kinoshita, Kunio Sato, Frank J.Gonzalez and Tetsuya Kamataki: "A new CYP2D6 allele with a nine base insertion in exon 9 in a Japanese population associated with poor metabolizer phenotype" Pharmacogenetics. 6. 395-401 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Katsunori Nakamura, Tsuyoshi Yokoi, Kazuaki Inoue, Noriaki Shimada, Noriko Ohashi, Toshiyuki Kume and Tetsuya Kamataki: "CYP2D6 in a principal cytochrome P450 responsible for metabolism of the histamine H1 antagonist promethazine in human liver microsomes" Pharmacogenetics. 6. 449-457 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nunoya et al.: "(+)-cis-3,5-dimethy 1-2-(3-pyridy) thiazolin-4-one Hydrochloride (SM-12502)as a novel substrate for cytochrome P450 2A6 (CYP2A6) in human liver microsomes." J. Pharmacal. Explt. Therap.277. 768-774 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yokoi et al.: "A new CYP2D6 allele with a nine base insertion in exon 9 in a Japanesepopulation associated with poor metabolizer phenotype." Pharmacogenetics. 6. 395-401 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakamura et al.: "CYP2D6 is a principal cytochrome P450 responsible for metabolism of the histamine H1 antagonist promethazine in human liver microsomes." Pharmacogenetics. 6. 449-457 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Takasuna et. al.: "Involvement of β-glucuronidase in intestinal microflora in intestinal toxicity of an antitumor camptothecin derivative irinotecan hydrochloride (CPT-11) in rats." Cancer Research. 56. 3752-3757 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Li et al.: "Perinatal Expression and inducibility of Human CYP3A7 in C57BL/6N Transgenic Mice." Biochem Biophys Res Commun. 228. 312-317 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Keiichi Nunoya et al.: "(+)-Cis-3,5-dimethyl-2-(3-pyridyl)thazolidin-4-one hydrochloride(SM-12502)as a novel substrate for cytochrome P450 2A6(CYP2a6)in human liver microsomes." J.Pharma.Exp.Ther.(in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] Miyuki Shimoji et al.: "Establishment of immortal hepatocytes from a CYP3A7-transgenic/p53-knockout mouse." Biochem.Biophys.Res.Commun.(in press).

    • Related Report
      1995 Annual Research Report
  • [Publications] Hisashi Hashimoto et al.: "Fetus-specific CYP3A7 and adult-specific CYP3A4 expressed in Chinese hamster CHL cells have similar capacity to activate carcinogenic mycotoxins." Cancer Res.55. 787-791 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tsuyoshi Yokoi et al.: "Occurrence of autoimmune antibodies to liver microsomal protein as the cause of lethal hepatitis in LEC rats:effects of TJN-101 on the development of hepatitis and the autoantibodies" Toxicology Letters,. 76. 33-38 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tsutomu Sakuma et al.,: "Efficient complementary DNA directed expression of human fetal liver cytochrome P450(CYP3A7)in insect cells using baculovirus." Biochem.Mol.Biol.Intem.35. 447-455 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tsutomu Sakuma et al.: "Isolation and characterization of a new cDNA clone belonging to the cytochrome P450 2C gene subfamily in hamsters." Arch.Biochem.Biophys.319. 267-273 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ken-ichi Nunoya et al.: "S-oxidation of (+)-cis-3,5-dimethyl-2-(3-pyridyl)thazolidin-4-one hydrochloride by hepatic rat flavin-containing monooxygenase 1 expressed in yeast." Xenobiotica. 25. 1283-1291 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tsuyoshi Yokoi et al.: "Inhibition of UDP-glucuronsyltransferase by aglycons of natural blucuronides in Kampo medicines using SN-38(7-ethyl-10-hydroxycamptothecin)as a substrate." Japn.J.Cancer Res.86. 985-989 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tsutomu Sakuma et al.: "Hormonal regulation of the mRNA level of male dominant cytochrome P450 (CYP2C27)in hamster livers." Pharmacol.Res.31. 371-374 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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