論文

査読有り
2005年1月

Lack of elevated liver carcinogenicity of aminophenylnorharman in p53-deficient mice

CANCER LETTERS
  • T Iidaka
  • ,
  • T Tsukamoto
  • ,
  • Y Totsuka
  • ,
  • A Hirata
  • ,
  • H Sakai
  • ,
  • N Shirai
  • ,
  • M Yamamoto
  • ,
  • K Wakabayashi
  • ,
  • T Yanai
  • ,
  • T Masegi
  • ,
  • LA Donehower
  • ,
  • M Tatematsu

217
2
開始ページ
149
終了ページ
159
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.canlet.2004.07.015
出版者・発行元
ELSEVIER SCI IRELAND LTD

The hepatocarcinogenic potential of 9-(4'-aminophenyl)-9H-pyrido[3,4-b]indole (aminophenylnorharman, APNH) was investigated using male and female p53 deficient mice. Incidence of oval cell hyperplasia was 2/14 (14.3%), 14/23 (60.9%), and 2/10 (20%) in p53 nullizygous (-/-), heterozygous (+/-), and wild type (+/+) mice, respectively, exposed to 30 ppm APNH for 15 weeks, while hepatocellular anisonucleosis was observed only in APNH-treated p53 (-/-) mice. At 40 weeks, hepatocellular carcinomas had developed in 16/46 (34.8%) and 10/27 (37.0%) of female p53 (+/-) and (+/+) mice in contrast to only 1/45 (2.2%) and 2/12 (16.7%) in their male counterparts, respectively, without any detectable p53 gene mutations. Dose-dependent APNH-DNA adduct formation and transcriptional induction of CYP 1A1, but not CYP 1A2, was revealed with 7-day APNH treatment using female C57BL/6J mice. These results suggested hepatocarcinogenicity of APNH in mice could be linked to the liver microenvironment including hormonal milieu but independent of p53 expression and p53 gene mutations. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

Web of Science ® 被引用回数 : 6

リンク情報
DOI
https://doi.org/10.1016/j.canlet.2004.07.015
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/15617832
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000226476800003&DestApp=WOS_CPL