Skip Navigation



Carcinogenesis Advance Access published online on June 13, 2006
Carcinogenesis, doi:10.1093/carcin/bgl080
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
27/8/1517    most recent
bgl080v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Di Pace, R. F.
Right arrow Articles by Ibañez, O. C. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Di Pace, R. F.
Right arrow Articles by Ibañez, O. C. M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
Received September 22, 2005
Revised April 11, 2006
Accepted May 16, 2006

CARCINOGENESIS

Inverse genetic predisposition to colon vs. lung carcinogenesis in mouse lines selected based on acute inflammatory responsiveness

Roberto Francisco Di Pace 1, Solange Massa 1, Orlando Garcia Ribeiro 1, Wafa Hanna Koury Cabrera 1, Marcelo De Franco 1, Nancy Starobinas 1, Michel Seman 2, and Olga Célia Martinez Ibañez 1 *

1 Laboratório de Imunogenética, Instituto Butantan, São Paulo, SP, Brazil
2 Laboratoire d'Immunodifférentiation, EA 1556, Université Denis Diderot, Paris, France

* To whom correspondence should be addressed.
Olga Célia Martinez Ibañez, E-mail: olgaibanez{at}butantan.gov.br


  Abstract

Mouse lines produced by bidirectional selection on the basis of maximum (AIRmax) or minimum (AIRmin) acute inflammatory reactions were examined for the development of chemically-induced acute colitis and colon tumors and the development of lung tumors. AIRmax mice were more susceptible than AIRmin to acute colitis induced by ingestion of dextran sodium sulfate showing a 3-fold higher disease activity index and presenting an intense inflammatory infiltrate in the base of colon crypts as well as elevated expression of IL-1{beta}, TNF{alpha}, IFN{gamma} and IL-6 mRNA in colon tissue. AIRmax were also more susceptible than AIRmin to colon cancer induced by 2 or 7 weekly doses of 1, 2 dimethylhydrazine (DMH), showing significantly higher numbers of colonic aberrant crypt foci (ACF) at 150 days after DMH treatment (p=0.01) and significantly higher numbers of tumors affecting larger intestinal areas at 300 to 475 days. At the latter time point, however, multiple lung adenomas and large adenocarcinomas were found in AIRmin but not in AIRmax mice. Treatment of mice with Nimesulide for 60 days beginning 24h before the first of two DMH doses almost completely inhibited the appearance of ACF in both lines. Furthermore, ACF numbers and the degree of acute inflammation directly co-segregated in an F2 (AIRmax x AIRmin) intercross population. The results demonstrate that genetic determinants of the inflammatory response differentially influence susceptibility to colon and lung carcinogenesis in the AIRmax and AIRmin mouse model.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.