The goal of the experimental animal core is to provide relevant mouse models to study colon tumor development and to study apoptosis in colon carcinogenesis. The mouse models will be used to evaluate genetic and extracellular factors (dietary polyamines, bile acids) that affect the apoptotic pathway and to evaluate the effects of potential chemopreventive agents. Included in these models are mice that have defective APC, p53, and NOS-2 genes, genes that have been shown or are hypothesized to be involved in the oncogenesis of colon tumors in both humans and mice. These models will allow further clarification of the biochemical mechanisms involved in colon carcinogenesis and will identify additional molecular targets for chemoprevention.
The specific aims of the core are: 1) to provide relevant murine models to study colon oncogenesis and the apoptotic pathway; 2) to provide treatments, carcinogens, and dietary supplements that promote tumor development in each appropriate model; 3) to administer chemopreventive agents; 4) to provide fresh tissues from the animal study protocols to each project; and 5) to perform gross and histologic analyses of intestinal tumors that develop in the murine models. The experimental animal core provides a means by which animals needed for studies in three different projects can be shared and the results of the studies are combinative. The advantages to having a experimental animal core are: less animals are needed than if each project performed the animal studies by themselves; there is uniformity and quality control in carrying out the study protocols across each project; data generated from each study is comparable given that the information is generated from the same sources with common controls; and the core allows examination of multiple rodent models of colon cancer that would otherwise be unaffordable or unavailable.
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