International Mammalian Genome Society


The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

E52 Genetic Analysis of Azoxymethane-Induced Colorectal Cancer

Pearsall, R. S.1, Cheraund, P.2, Hicks, D.1, Amann, V.1, Coffey, R.1,3, Caprioli, R.2 and Threadgill, D. W.1,3. 1Department of Cell Biology, 2Department of Biochemistry, 3Department of Medicine, Vanderbilt University Medical Center, Nashville, TN USA 37209

We are interested in using the mouse as a model system to study the development of colorectal cancer. We have administered azoxymethane (AOM), a potent carcinogen, to mice and are following the progression of the specific colorectal cancers which are formed. The tumors appear to follow a similar pattern of progression as human tumors, making this an attractive model system for further analysis. There is strain specific susceptibility to AOM treatment indicating the presence of genetic modifiers in different strains. We are analyzing the basis of AOM-induced colorectal cancer susceptibility in genetic crosses of mice with different susceptibilities. Also, in order to better define the molecular changes which are occurring during tumor progression we have begun using matrix-assisted laser desorption ionization mass spectronomy (MALDI MS) to analyze the compounds on the surface of tissue slices. The spectral patterns of both normal and cancerous tissues are quite reproducible, but are distinct from each other in the types of compounds present. We hope that this technique will be useful for developing a "fingerprint" of the types of compounds present in normal versus various tumor stages present in colorectal cancer. In addition, we are also using DNA microarray analysis to characterize changes occurring during tumor progression. The use of micorarrays can help identify changes in both DNA copy number and RNA expression levels between normal and various stage tumors. We have currently identified AOM susceptible and resistant strains of mice and have begun the analysis of intercross and backcross progeny. We have begun a strain specific comparison of colonic tissue using the MALDI mass spectronomy analysis. We have also begun assembling and manufacturing microarray slides for expression and DNA assays.

 


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