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

开发用于不使用动物的毒理学研究的细胞色素 P-450 工艺

• 批准号: 08456155
• 负责人: KAZUSAKA Akio
• 金额: $ 4.03万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08456155/
• 关键词: TOXICOLOGICAL 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

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.

显然，某些农业医学，医学，食品添加剂或化学产品将环境污染为​​环境激素。但是，毒理学评估技术尚未确定。特别是有一些技术可以估计代谢产物的毒性，这些技术被代谢酶激活为细胞色素P450。最近指出，应该再次估算许多化学物质。因此，有必要开发新技术来评估许多化学物质。因此，本项目涉及细胞色素P450的发展，用于研究毒理学研究，而无需将动物作为小鼠或大鼠。已经进行了几项实验，以研究实验室中细胞色素P-450对异种生物的酶促分析（1），在自然领域（2），通过分子生物学技术（3）表达，或使用光谱技术（4）。每个结果都在几本期刊上发表。应该强调的是，在NoInsistive评估中已经开发了新技术来使用光谱法。

项目成果

Tasaki, T. , et al.: "Expression and characterization of dog CYP2D15 using baculovirus expression system1." J.Biochem.123. 162-168 (1998)

Tasaki, T. 等人：“使用杆状病毒表达系统表达和表征狗 CYP2D151。”

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)

Yamamoto, Y.、Tasaki, T.、Nakamura, A.、Iwata, H.、Kazusaka, A.、Gonzalezb, F.J.、Fujita, S.：“暗刺豚鼠药物氧化多态性的分子基础：CYP2D1 和

Tasaki,T.et al.: "Regio-and stereoselectivity in propranolol metabolism by dog liver microsomes and dog CYP2D15." J.Biochem.(in press). (1998)

Tasaki,T.et al.：“狗肝微粒体和狗 CYP2D15 普萘洛尔代谢的区域选择性和立体选择性。”

Maeda, Y.: "Strain differences in testosterone metabolism in Wister and Dark Agouti rats -A new polymorphism-" Environ.Toxicol.Pharmacol.(in press). (1997)

Maeda, Y.：“Wister 和 Dark Agouti 大鼠睾酮代谢的菌株差异 - 一种新的多态性 -”Environ.Toxicol.Pharmacol.（出版中）。

Yamamoto,Y.et al.: "Molecular basis of the Dark Agouti rat drug oxidation polymorphism:lnvolvement of CYP2D1 and CYP2D2." Pharmacogenetics. (in press). (1998)

Yamamoto,Y.et al.：“Dark Agouti 大鼠药物氧化多态性的分子基础：CYP2D1 和 CYP2D2 的参与。”