BACKGROUND: Several animal models for human ulcerative colitis (UC) associated neoplasia have been reported. However, most neoplasias developed in these models have morphological and genetic characteristics different from UC associated neoplasia. AIMS: To establish a new colitis associated neoplasia model in p53 deficient mice by treatment with dextran sulphate sodium (DSS). METHODS: DSS colitis was induced in homozygous p53 deficient mice (p53(-/-)-DSS), heterozygous p53 deficient mice (p53(+/-)-DSS) and wild-type mice (p53+/+-DSS) by treatment with 4% DSS. Numbers of developed neoplasias were compared among the experimental groups, and macroscopic and microscopic features of the neoplasias were analysed. Furthermore, K-ras mutation and beta-catenin expression were assessed. RESULTS: p53(-/-)-DSS mice showed 100% incidence of neoplasias whereas the incidences in p53(+/-)-DSS and p53+/+-DSS mice were 46.2% and 13.3%, respectively. No neoplasias were observed in the control groups. The mean numbers of total neoplasias per mouse were 5.0 (p53(-/-)-DSS), 0.62 (p53(+/-)-DSS), and 0.2 (p53+/+-DSS). The number of neoplasias per mouse in the p53(-/-)-DSS group was significantly higher than that in the other DSS groups. The incidences of superficial type neoplasias were 91.7% in p53(-/-)-DSS mice, 75.0% in p53(+/-)-DSS mice, and 33.3% in p53+/+-DSS mice. The K-ras mutation was not detected in any of the neoplasias tested. Translocation of beta-catenin from the cell membrane to the cytoplasm or nucleus was observed in 19 of 23 (82.6%) neoplasias. CONCLUSIONS: The p53(-/-)-DSS mice is an excellent animal model of UC associated neoplasia because the morphological features and molecular genetics are similar to those of UC associated neoplasia. Therefore, this model will contribute to the analysis of tumorigenesis related to human UC associated neoplasia and the development of chemopreventive agents.
BACKGROUND: Several animal models for humanulcerative colitis (UC) associated neoplasia have been reported. However, most neoplasias developed in these models have morphological and genetic characteristics different from UC associated neoplasia. AIMS: To establish a new colitis associated neoplasia model in p53 deficient mice by treatment with dextran sulphate sodium (DSS). METHODS:DSScolitis was induced in homozygous p53 deficient mice (p53(-/-)-DSS), heterozygous p53 deficient mice (p53(+/-)-DSS) and wild-type mice (p53+/+-DSS) by treatment with 4% DSS. Numbers of developed neoplasias were compared among the experimental groups, and macroscopic and microscopic features of the neoplasias were analysed. Furthermore, K-ras mutation and beta-catenin expression were assessed. RESULTS:p53(-/-)-DSSmice showed 100% incidence of neoplasias whereas the incidences in p53(+/-)-DSS and p53+/+-DSSmice were 46.2% and 13.3%, respectively. No neoplasias were observed in the control groups. The mean numbers of total neoplasias per mouse were 5.0 (p53(-/-)-DSS), 0.62 (p53(+/-)-DSS), and 0.2 (p53+/+-DSS). The number of neoplasias per mouse in the p53(-/-)-DSS group was significantly higher than that in the other DSS groups. The incidences of superficial type neoplasias were 91.7% in p53(-/-)-DSSmice, 75.0% in p53(+/-)-DSSmice, and 33.3% in p53+/+-DSSmice. The K-ras mutation was not detected in any of the neoplasias tested. Translocation of beta-catenin from the cell membrane to the cytoplasm or nucleus was observed in 19 of 23 (82.6%) neoplasias. CONCLUSIONS: The p53(-/-)-DSSmice is an excellent animal model of UC associated neoplasia because the morphological features and molecular genetics are similar to those of UC associated neoplasia. Therefore, this model will contribute to the analysis of tumorigenesis related to human UC associated neoplasia and the development of chemopreventive agents.
Authors: R J Schlemper; R H Riddell; Y Kato; F Borchard; H S Cooper; S M Dawsey; M F Dixon; C M Fenoglio-Preiser; J F Fléjou; K Geboes; T Hattori; T Hirota; M Itabashi; M Iwafuchi; A Iwashita; Y I Kim; T Kirchner; M Klimpfinger; M Koike; G Y Lauwers; K J Lewin; G Oberhuber; F Offner; A B Price; C A Rubio; M Shimizu; T Shimoda; P Sipponen; E Solcia; M Stolte; H Watanabe; H Yamabe Journal: Gut Date: 2000-08 Impact factor: 23.059
Authors: D E Aust; J P Terdiman; R F Willenbucher; K Chew; L Ferrell; C Florendo; A Molinaro-Clark; G B Baretton; U Löhrs; F M Waldman Journal: Mod Pathol Date: 2001-01 Impact factor: 7.842
Authors: S P Hussain; P Amstad; K Raja; S Ambs; M Nagashima; W P Bennett; P G Shields; A J Ham; J A Swenberg; A J Marrogi; C C Harris Journal: Cancer Res Date: 2000-07-01 Impact factor: 12.701
Authors: Yu Jin; Anne B Hofseth; Xiangli Cui; Anthony J Windust; Deepak Poudyal; Alex A Chumanevich; Lydia E Matesic; Narendra P Singh; Mitzi Nagarkatti; Prakash S Nagarkatti; Lorne J Hofseth Journal: Cancer Prev Res (Phila) Date: 2010-02-23
Authors: Daniel A Sussman; Rebeca Santaolalla; Sebastian Strobel; Rishu Dheer; Maria T Abreu Journal: Curr Opin Gastroenterol Date: 2012-07 Impact factor: 3.287
Authors: Pallavi Garg; Sabrina Jeppsson; Guillaume Dalmasso; Amr M Ghaleb; Beth B McConnell; Vincent W Yang; Andrew T Gewirtz; Didier Merlin; Shanthi V Sitaraman Journal: Gastroenterology Date: 2011-06-30 Impact factor: 22.682