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DEVELOPMENT OF CYTOCHROME P-450 PROCESS FOR THE STUDY OF TOXICOLOGY WITHOUT USING ANIMALS

Research Project

Project/Area Number 08456155
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied veterinary science
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

KAZUSAKA Akio  GRADUATE SCHOOL OF VETERINARY MEDICINE,HOKKAIDO UNIV., ASSOCIATE PROFESSOR, 大学院・獣医学研究科, 助教授 (00002113)

Co-Investigator(Kenkyū-buntansha) IWATA Hisato  GRADUATE SCHOOL OF VETERINARY MEDICINE,HOKKAIDO UNIV., INSTRUCTOR, 大学院・獣医学研究科, 助手 (10271652)
FUJITA Shoichi  GRADUATE SCHOOL OF VETERINARY MEDICINE,HOKKAIDO UNIV., PROFESSOR, 大学院・獣医学研究科, 教授 (10143314)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1996: ¥2,500,000 (Direct Cost: ¥2,500,000)
KeywordsTOXICOLOGICAL ASSESSMENT / ANIMAL SUBSTITUTION / CYTOCHROME P450 / ENZYMATIC ANALYSIS / MOLECULAR BIOLOGICAL METHOD / SPECTROSCOPIC METHOD / NONINVASIVE ASSESSMENT / 遺伝子組み替え / CYPIID / イヌCYPII D15 / 海棲哺乳動物CYP1A / Sf9細胞 / チトクロムP450IID / イヌP450IID15 / バキュロウイルス / P450酵素反応 / P450-2D / 組み替えP450の発現 / 光ファイバー検出系 / P450-1A / エトキシゾルフィン / レゾルフィン
Research Abstract

It is getting clear that some agricultural medicine, medicine, food additive or chemical product contaminates environment as an environmental hormone. Toxicological assessment technique, however, has not established about them. Especially there is a few technology to estimate toxicity of metabolites, which are activated by metabolic enzyme as cytochrome P450. It is pointed out recently that many chemicals should be estimated again. Therefore it is necessary to develop new technique to assess many chemicals. The present project is thus concerned with the development of cytochrome P450 process for the study of toxicology without using animals as mice or rats. Several experiments have been carried out to study an enzymatic analysis of cytochrome P-450 to xenobiotics in laboratory (1), in natural field (2), expressed by molecular biological technique (3), or using spectroscopic technique (4). Each result has been published in several journal. It should be stressed that new technique has been developed in noinvasive assessment to use spectroscopic method.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Ishizuka, M. , et al.: "Accumulation of halogenated aromatic hydrocarbons and activities of cytochrome P450 and glutathione S-transferase in crabs(eriocheir japonicus) from japanese rivers." Environmental Toxicology and Chemistry. 17. 1490-1498 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tasaki, T. , et al.: "Expression and characterization of dog CYP2D15 using baculovirus expression system1." J.Biochem.123. 162-168 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamamoto, Y. , et al.: "Molecular basis of the dark agouti rat drug oxidation polymorphism : importance of CYP2D1 and CYP2D2." Pharmacologenetics. 8. 73-82 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tasaki, T. , et al.: "Regio‐ and stereoselectivity in propranolol metabolism by dog liver microsomes and the dog CYP2D151." J.Biochem.123. 747-751 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Morita, K. , et al.: "Strain differences in CYP3A-mediated C-8 Hydroxylation(1, 3, 7-Trimethyluric acid formation) of caffeine in wistar and dark agouti rats." Biochemical Pharmacology. 55. 1405-1411 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shimamoto, Y. , et al.: "Differetial alterations in levels of hepatic microsomal cytochrome P450 isozymes following intracerebroventricular injection of bacterial lipopolysaccharide in rats." Arch Toxicol. 72. 492-498 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ishizuka, M., Sakiyama, T., Iwata, H., Fukushima, M., Kazusaka, A., Fujita, S.: "Accumulation of halogenated aromatic hydrocarbons and activities of cytochrome P450 and glutathione S-transferase in crabs (eriocheir japonicus) from japanese rivers." Environmental Toxicology and Chemistry. 17. 1490-1498 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tasaki, T., Nakamura, A., Itoh, S., Ohashi, K., Yamamoto, Y., Masuda, M., Iwata, H., Kazusaka, A., Kamataki, T., Fujita, S.: "Expression and characterization of dog CYP2D15 using baculovirus expression system." J.Biochem. 123. 162-168 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamamoto, Y., Tasaki, T., Nakamura, A., Iwata, H., Kazusaka, A., Gonzalezb, F.J., Fujita, S.: "Molecular basis of the dark agouti rat drug oxidation polymorphism : importance of CYP2D1 and CYP2D2." Pharmacologenetics. 8. 73-82 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tasaki, T., Iwata, H., Kazusaka, A., Fujita, S.: "Regio- and stereoselectivity in propranolol metabolism by dog liver microsomes and dog CYP2D15." J.Biochem. 123. 747-751 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Morita, K., Maeda, Y., Masuda, M., Kazusaka, A., Fujita, S.: "Strain differences in CYP3A-mediated C-8 hydroxylation (1,3,7-trimethyluric acid formation) of caffeine in Wistar and Dark Agouti rats." Environ.Sci.Technol.32. 2244-2249 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shimamoto, Y., Kitamura, H., Hoshi, H., Kazusaka, A., Funae, Y., Imaoka, S., Saito, M., Fujita, S.: "Differential alteration of microsomal cytochrome P450 levels in rat liver microsomes following intracerebral injection of bacterial lipopolysaccharide." Archive of Toxicology. 72. 492-498 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ishizuka,M.et al.: "Accumulation of halogenated aromatic hydrocarbons and activities of cytochrome P450 and glutathione S-transferase in crabs(enocheir japonicus)from japanese rivers." Environmental Toxicology and Chemistry. 17. 1490-1498 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tasaki,T.et al.: "Expression and characterization of dog CYP2D15 using baculovirus expression system1." J.Biochem.123. 162-168 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamamoto,Y.et al.: "Molecular basis of the dark agouti rat drug oxidation polymorphism: importance of CYP2D1 and CYP2D2." Pharmacologenetics. 8. 73-82 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tasaki,T.et al.: "Regio- and stereoselectivity in propranolol metabolism by dog liver microsomes and the dog CYP2D151." J.Biochem.123. 747-751 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Morita,K.et al.: "Strain differences inCYP3A-mediated C-8 Hydroxylation(1,3,7-Trimethyluric acid formation)of caffeine in wistar and dark agouti rats." Biochemical Pharmacology. 55. 1405-1411 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shimamoto,Y.et al.: "Differetial alterations in levels of hepatic microsomal cytochrome P450 isozymes following intracerebroventricular injection of bacterial lipopolysaccharide in rats." Arch Toxicol.,. 72. 492-498 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tasaki,T.et al.: "Expression and characterization of dog CYP2D15 using baculovirus expression system." J.Biochem.123. 162-168 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tasaki,T.et al.: "Regio-and stereoselectivity in propranolol metabolism by dog liver microsomes and dog CYP2D15." J.Biochem.(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yamamoto,Y.et al.: "Molecular basis of the Dark Agouti rat drug oxidation polymorphism:lnvolvement of CYP2D1 and CYP2D2." Pharmacogenetics. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Maeda,Y.et al.: "Strain differences in testosterone metabolism in Wister and Dark Agouti rats -A new polymorphism-." Environ.Toxicol.Pharmacol.3. 1-6 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ishizuka,M.et al.: "Pathway-selective alteration of imipramine metabolism during regeneration of male rat liver followeing partial hepatectomy." Xenobiotica. 27. 923-931 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoon,S-J et al.: "Esr and infreared spectroscopic characterization of the toxic radical formed in the liver of the SD rats impaired with CCl_4." Proc.2nd intl.conf.bioradicals and 5th intl.workshop on esr(epr)imaging and in vivo esr spectroscopy. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ishizuka, M.: "Alteration of cytochrome P450 dependent monooxygenase activities in Eriocheir japonicus in response to water pollution" Environ.Health Perspec.104・7. 774-778 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yamamoto, Y.: "Impaired expression in rats of catalytically active P450BTL, immunochemically distinguishable from P4502D1 : Immunological evidence with specific anti-peptide antibody" Biomedical Research. 17・5. 331-337 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hatakeyama, S.: "Mechanism for mouse strain defferences in the protective effect of Sudan III against the in vivo genotoxicity of 7, 12-dimethylbenz (a) anthracene" Toxicology Letters. 89. 231-239 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Maeda, Y.: "Strain differences in testosterone metabolism in Wister and Dark Agouti rats -A new polymorphism-" Environ.Toxicol.Pharmacol.(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Iwata, H.: "Bioaccumulation of butyltin compounds in marine mammals : Their tissue distribution and composition" Appl.Organomet.Chem.(in press). (1997)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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