Item type |
学術雑誌論文 / Journal Article(1) |
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
Itoh, Masahiro
Sakai, Haruko
Fukami, Tatsuki
Kato, Miki
Yamazaki, Hiroshi
Kadlubar, Fred F.
Imaoka, Susumu
Funae, Yoshihiko
Yokoi, Tsuyoshi
|
著者別表示 |
中嶋, 美紀
深見, 達基
山崎, 浩史
|
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
|
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 |