論文

査読有り
2007年8月

Organ-dependent susceptibility of p53 knockout mice to 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)

CANCER SCIENCE
  • Akihiro Hirata
  • ,
  • Tetsuya Tsukamoto
  • ,
  • Masami Yamamoto
  • ,
  • Shinji Takasu
  • ,
  • Hiroki Sakai
  • ,
  • Hisayo Ban
  • ,
  • Tokuma Yanai
  • ,
  • Toshiaki Masegi
  • ,
  • Lawrence A. Donehower
  • ,
  • Masae Tatematsu

98
8
開始ページ
1164
終了ページ
1173
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1111/j.1349-7006.2007.00517.x
出版者・発行元
BLACKWELL PUBLISHING

p53 knockout mice are now being frequently used to identify the carcinogenic potential of chemicals, thus it is important to precisely assess the susceptibility of the animals to various test chemicals. In the present study the susceptibility of p53 nullizygous((-/-)), heterozygous((+/-)), and wild-type((+/+)) mice to 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) was investigated. Mice of all three genotypes were first fed a diet containing 100 or 300 p.p.m. IQ for 15 weeks in a short-term experiment. p53((+/-)) and ((+/+)) mice were then treated with IQ for 40 weeks and maintained without further treatment for an additional 12 weeks in the long-term experiment. In the forestomach, the incidence of squamous cell hyperplasia was significantly higher in p53((-/-)) than in ((+/-)) and ((+/+)) mice at 15 weeks and higher in ((+/-)) mice than ((+/+)) mice with long-term IQ treatment, indicating an elevated susceptibility of p53 knockout mice. In contrast, in the liver, various hepatocellular lesions developed mainly in female mice with long-term IQ exposure but no significant differences were evident between p53 knockout and wild-type mice, indicating a lack of elevated susceptibility in the knockout animals. Furthermore, polymerase chain reaction-single strand conformation polymorphism and sequencing analysis revealed relatively high (13/30) and low (1/15) incidences of p53 mutations (exons 5-8) in squamous cell hyperplasia and hepatocellular tumors, respectively. These results clearly indicate that the susceptibility of p53 knockout mice is organ-dependent, coinciding to some extent with the likelihood of p53 gene alteration in the induced tumors.

Web of Science ® 被引用回数 : 1

リンク情報
DOI
https://doi.org/10.1111/j.1349-7006.2007.00517.x
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/17532756
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000247560900005&DestApp=WOS_CPL