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CYP2A13 expressed in human bladder metabolically activates 4-aminobiphenyl
https://doi.org/10.24517/00014876
https://doi.org/10.24517/00014876c2203452-70c3-4767-b9ec-82974c7f70c3
名前 / ファイル | ライセンス | アクション |
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PH-PR-NAKAJIMA-M-2520.pdf (554.0 kB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2017-10-03 | |||||
タイトル | ||||||
タイトル | CYP2A13 expressed in human bladder metabolically activates 4-aminobiphenyl | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
ID登録 | ||||||
ID登録 | 10.24517/00014876 | |||||
ID登録タイプ | JaLC | |||||
著者 |
Nakajima, Miki
× Nakajima, Miki× Itoh, Masahiro× Sakai, Haruko× Fukami, Tatsuki× Kato, Miki× Yamazaki, Hiroshi× Kadlubar, Fred F.× Imaoka, Susumu× Funae, Yoshihiko× Yokoi, Tsuyoshi |
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著者別表示 |
中嶋, 美紀
× 中嶋, 美紀× 深見, 達基× 山崎, 浩史 |
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提供者所属 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 金沢大学ナノ生命科学研究所 / 金沢大学大学院医学系研究科機能分子医薬学 / 金沢大学薬学部 | |||||
書誌情報 |
International Journal of Cancer 巻 119, 号 11, p. 2520-2526, 発行日 2006-01-01 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0020-7136 | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1002/ijc.22136 | |||||
出版者 | ||||||
出版者 | Wiley-Liss | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Cigarette smoking is the predominant risk factor for bladder cancer. Aromatic amines such as 4-aminobiphenyl (ABP) is the major carcinogens found in tobacco smoke. Although it is generally accepted that ABP is metabolically activated via N-hydroxylation by CYP1A2 in human liver, previous studies using Cyp1a2-null mice indicated the involvement of other enzyme(s). Here we found that CYP2A13 can metabolically activate ABP to show genotoxicity by Umu assay. The Km and Vmax values for ABP N-hydroxylation by recombinant CYP2A13 in E. coli were 38.5 ± 0.6 μM 7.8 ± 0.0 pmol/min/pmol CYP, respectively. The Km and Vmax values by recombinant CYP1A2 were 9.9 ± 0.9 μM and 39.6 ± 0.9 pmol/min/ pmol CYP, respectively, showing 20-fold higher intrinsic clearance than CYP2A13. In human bladder, CYP2A13 mRNA, but not CYP1A2, is expressed at a relatively high level. Human bladder microsomes showed ABP N-hydroxylase activity (K m = 34.9 ± 4.7 μM and Vmax = 57.5 ± 1.9 pmol/min/mg protein), although the intrinsic clearance was 5-fold lower than that in human liver microsomes (Km = 33.2 ± 2.0 μM and Vmax = 293.9 ± 5.8 pmol/min/mg protein). The activity in human bladder microsomes was prominently inhibited by 8-methoxypsoralen, but not by fluvoxamine, anti-CYP1A2 or anti-CYP2A6 antibodies. | |||||
著者版フラグ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa |