Azoxymethane Is a Genetic Background-Dependent Colorectal Tumor Initiator and Promoter in Mice: Effects of Dose, Route, and Diet
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 o...
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Published in | Toxicological sciences Vol. 88; no. 2; pp. 340 - 345 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
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United States
Oxford University Press
01.12.2005
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Abstract | 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. |
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AbstractList | 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. |
Author | Bissahoyo, Anika Pearsall, R. Scott Hicks, Donna Godfrey, Virginia L. Amann, Vicky Threadgill, David W. Hanlon, Kathleen |
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BackLink | https://www.ncbi.nlm.nih.gov/pubmed/16150884$$D View this record in MEDLINE/PubMed |
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Notes | ark:/67375/HXZ-LWQW6VB7-Q 1To whom correspondence should be addressed at Department of Genetics, CB#7294, MBRB 4340, University of North Carolina, Chapel Hill, NC 27599. Fax: (919) 966-3292. E-mail: dwt@med.unc.edu. local:kfi313 istex:22A389C5D836F0F254A0A8771255408A09F87162 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
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SubjectTerms | Adenocarcinoma - chemically induced Adenocarcinoma - genetics Adenocarcinoma - pathology Animals azoxymethane Azoxymethane - administration & dosage Azoxymethane - toxicity Carcinogens - administration & dosage Carcinogens - toxicity Colon - drug effects Colon - pathology Colorectal Neoplasms - chemically induced Colorectal Neoplasms - genetics Colorectal Neoplasms - pathology colorectal tumorigenesis Crosses, Genetic Diet Disease Models, Animal dose curve Dose-Response Relationship, Drug Drug Administration Routes Female Gene Expression Regulation, Neoplastic Genetic Predisposition to Disease genetic susceptibility Male Mice Mice, Inbred C57BL Mice, Inbred DBA Pregnancy Research Design - standards Species Specificity |
Title | Azoxymethane Is a Genetic Background-Dependent Colorectal Tumor Initiator and Promoter in Mice: Effects of Dose, Route, and Diet |
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