CYP2A13 expressed in human bladder metabolically activates 4-aminobiphenyl

フォーマット:

論文

責任表示:

Nakajima, Miki ; Itoh, Masahiro ; Sakai, Haruko ; Fukami, Tatsuki ; Kato, Miki ; Yamazaki, Hiroshi ; Kadlubar, Fred F. ; Imaoka, Susumu ; Funae, Yoshihiko ; Yokoi, Tsuyoshi

言語:

英語

出版情報:

Wiley-Liss, 2006-01-01

著者名:

Nakajima, Miki

Itoh, Masahiro

Sakai, Haruko

Fukami, Tatsuki

Kato, Miki

Yamazaki, Hiroshi

Kadlubar, Fred F.

Imaoka, Susumu

Funae, Yoshihiko

Yokoi, Tsuyoshi

続きを見る

掲載情報:

International Journal of Cancer

ISSN:

0020-7136      

巻:

119

通号:

11

開始ページ:

2520

終了ページ:

2526

概要:

金沢大学大学院医学系研究科機能分子医薬学<br />金沢大学薬学部<br />author<br />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. Althoug … h 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. 続きを見る

URL:

http://hdl.handle.net/2297/6678