Pharmacogenetics of drug metabolizing enzymes

药物代谢酶的药物遗传学

• 批准号: 07672337
• 负责人: YOKOI Tsuyoshi
• 金额: $ 1.41万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07672337/
• 关键词: genotyping; 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

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.

研究CYP 2A 6基因多态性。发现（+）-顺式-3，5-二甲基-2-（3-吡啶基）噻唑烷-4-酮盐酸盐（SM-12502）是CYP 2A 6的特异性底物。以CYP 2A 6cDNA为探针，对SM-12502强代谢型和弱代谢型（PM）的基因组DNA进行Southern印迹分析。研究了一种新的区分PM的Sac I-RELP。最后，我们得出结论，SM-12502的PM负责CYP 2A 6全基因缺失。建立了一种新的CYP 2A 6全基因缺失PCR分型方法。

项目成果

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 as

Tsuyoshi Yokoi、Yasuyuki Kosaka、Michihiro Chiba、Kan Chiba、Hidefumi Nakamura、Takashi Ishizaki、Moritoshi Kinoshita、Kunio Sato、Frank J.Gonzalez 和 Tetsuya Kamataki：“在日本人群中，一个新的 CYP2D6 等位基因在外显子 9 中插入了 9 个碱基，

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)

H. Hashimoto：“中国仓鼠 CHL 细胞中表达的胎儿特异性 CY P3A7 和成人特异性 CYP3A4 具有相似的激活致癌霉菌毒素的能力。”

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)

T. Sakuma：“仓鼠中属于 oytochrome P450 2C 基因亚家族的新 cDNA 是否已完成解析和表征。”

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

Katsunori Nakamura、Tsuyoshi Yokoi、Kazuaki Inoue、Noriaki Shimada、Noriko Ohashi、Toshiyuki Kume 和 Tetsuya Kamataki：“主要细胞色素 P450 中的 CYP2D6 负责人肝微粒体中组胺 H1 拮抗剂异丙嗪的代谢

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)

Tsutomu Sakuma 等人：“使用杆状病毒在昆虫细胞中高效互补 DNA 指导表达人胎肝细胞色素 P450 (CYP3A7)。”