Non-synonymous Single Nucleotide Alterations Found in the CYP2C8 Gene Result in Reduced in Vitro Paclitaxel Metabolism
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概要
- 論文の詳細を見る
By sequencing genomic DNA from 73 established cell lines derived from Japanese individuals, we detected 9 single nucleotide polymorphisms(SNPs)in the CYP2C8 gene. Of them, 3 exonic SNPs resulted in amino acid alterations(g416a, R139K; a1196g, K399R; c1210g, P404A). The first two alterations were detected concurrently in one cell line and thought to be the same as CYP2C8^*3. To examine the effects of these amino acid alterations on CYP2C8 function, wild-type and four types of variant CYP2C8 cDNA constructs(R139K, K399R, R139K/K399R and P404A)were transfected into Hep G2 cells and their paclitaxel 6α-hydroxylase activities were determined in vitro. K_m values were not significantly different from that of the wild-type in any of the variants studied. The variant R139K/K399R showed reduced values for V_<max> and clearance(V_<max>/K_m)similar to those of its single variant, R139K. The variant P404A also showed a significantly lowered clearance due to reduced level of protein expression. These results suggest that not only the double variant(R139K/K399R, CYP2C8^*3)but also our novel variant P404A in the CYP2C8 gene are less efficient in paclitaxel metabolism.
- 社団法人日本薬学会の論文
- 2001-12-01
著者
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SAITO Yoshiro
Project Team for Pharmacogenetics, National Institute of Health Sciences
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OZAWA Shogo
Project Team for Pharmacogenetics, National Institute of Health Sciences
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SAWADA Jun-ichi
Project Team for Pharmacogenetics, National Institute of Health Sciences
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Kaniwa N
Department Of Genome Biology Kinki University School Of Medicine
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SAI Kimie
Project team for Pharmacogenetics, National Institute of Health Sciences
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Sai Kimie
Project Team For Pharmacogenetics National Institute Of Health Sciences
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KATORI Noriko
Project team for Pharmacogenetics, National Institute of Health Sciences
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SOYAMA Akiko
Project Team for Pharmacogenetics, National Institute of Health Sciences
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HANIOKA Nobumitsu
Project Team for Pharmacogenetics, National Institute of Health Sciences
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MURAYAMA Norie
Project Team for Pharmacogenetics, National Institute of Health Sciences
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NAKAJIMA Osamu
Division of Biochemistry and Immunochemistry National Institute of Health Sciences
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ISHIDA Seiichi
Project Team for Pharmacogenetics, National Institute of Health Sciences
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Katori Noriko
Project Team For Pharmacogenetics National Institute Of Health Sciences
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Murayama N
Division Of Xenobiotic Metabolism And Disposition
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Murayama Norie
Project Team For Pharmacogenetics National Institute Of Health Science
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中島 修
東京大学分子細胞生物学研究所
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NISHIO Kazuto
Department of Genome Biology, Kinki University School of Medicine
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Nishio K
Department Of Genome Biology Kinki University School Of Medicine
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Soyama A
Project Team For Pharmacogenetics National Institute Of Health Sciences
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Soyama Akiko
Project Team For Pharmacogenetics National Institute Of Health Sciences
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Yoshida Shigeaki
国立がんセンター東病院 消化管内科
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Kuzuya Nobuaki
国立医薬食品衛生研究所 薬物応答予測プロジェクト
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Ishida Seiichi
Division of Pharmacology, National Institute of Health Sciences
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Ozawa Shogo
National Institute Of Health Sciences
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Nakajima Osamu
National Inst. Of Health Sciences
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Ishida Seiichi
Division Of Pharmacology National Institute Of Health Sciences
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Ishida Seiichi
National Institute Of Health Sciences
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NAKATA Kotoko
National Institute of Health Sciences
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Sawada Jun-ichi
Project Team For Pharmacogenetics National Institute Of Health Science
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Hanioka Nobumitsu
Project Team For Pharmacogenetics National Institute Of Health Sciences:division Of Environmental Ch
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Ozawa Shogo
Project Team For Pharmacogenetics National Inst. Of Health Sciences
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Sawada J
Mie Univ. School Of Medicine Mie Jpn
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Okada Shuichi
Hepatobiliary And Pancreatic Oncology Division National Cancer Center Hospital
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Ozawa Shogo
Project Team For Pharmacogenetics
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