Journal
TOXICOLOGICAL SCIENCES
Volume 88, Issue 2, Pages 340-345Publisher
OXFORD UNIV PRESS
DOI: 10.1093/toxsci/kfi313
Keywords
azoxymethane; dose curve; colorectal tumorigenesis; genetic susceptibility
Categories
Funding
- NCI NIH HHS [CA79869, CA68485, CA16086, CA106991] Funding Source: Medline
- NIEHS NIH HHS [ES11391, ES10126, ES012354] Funding Source: Medline
Ask authors/readers for more resources
The azoxymethane (AOM) model has been widely used to investigate the pathology and genetics of colorectal cancer in rodents. However, there has been wide variation in treatment regimes, making it difficult to compare across studies. Consequently, standardizing AOM treatment and identifying sources of experimental variation would allow better comparisons across studies. In order to establish an optimal dosing regime for detecting experiment-dependent differences in tumorigenesis, we performed a dose curve analysis using AKR/J, SWR/J, and A/J mouse strains previously reported to vary widely in susceptibility to AOM. Although intraperitoneal or subcutaneous administration, but not in utero exposure, resulted in similar levels of tumor induction, significant dose- and strain-dependent effects of AOM were observed. No sex-dependent differences were observed. Increasing the number of treatments uncovered a significant strain-dependent effect on tumor promotion, independent of susceptibility to tumor initiation. Similarly, we used C57BL/6J and DBA/2J intercrosses to demonstrate that small diet modifications can significantly alter AOM-induced tumorigenesis in a background-dependent manner. These results provide experimental support for a standardized AOM treatment and for the importance of controlling both genetic and non-genetic factors when using this model.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available