1998 Fiscal Year Final Research Report Summary
DEVELOPMENT OF CYTOCHROME P-450 PROCESS FOR THE STUDY OF TOXICOLOGY WITHOUT USING ANIMALS
| Project/Area Number |
08456155
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied veterinary science
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| Research Institution | HOKKAIDO UNIVERSITY |
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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)
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| 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)
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| Project Period (FY) |
1996 – 1998
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| Keywords | TOXICOLOGICAL ASSESSMENT / ANIMAL SUBSTITUTION / CYTOCHROME P450 / ENZYMATIC ANALYSIS / MOLECULAR BIOLOGICAL METHOD / SPECTROSCOPIC METHOD / NONINVASIVE ASSESSMENT |
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| 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.
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[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)
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[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)
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[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)
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[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)
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[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)
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「研究成果報告書概要(欧文)」より
