Open Access Analysis of -Catenin, Ki-ras, and Microsatellite Stability in Azoxymethane-Induced Colon Tumors of BDIX/Orl Ico Rats

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Abstract:

The aim of the study reported here was to investigate whether the azoxymethane (AOM)-induced colon cancer rat model mimics the human situation with regard to microsatellite stability, changes in expression of -catenin, and/or changes in the sequence of the proto-oncogene Ki-ras. Colon cancer was induced by administration of four weekly doses of AOM (15 mg/kg of body weight per week) separated by a one-week break between the second and third injections. As the histopathologic characteristics of this model resemble those of the human counterpart, further characterization of the genetic changes was undertaken. The animals were euthanized 28 to 29 weeks after the first AOM injection, and tumor specimens were taken for histologic and DNA analyses. Since microsatellite variation was found in only a few (< 2%) specimens, the model can be considered as having stable microsatellites. This result is in accordance with those of similar studies in other rat models and with most human colorectal cancers. Immunohistochemical analyses of -catenin did not reveal loss of gene activity, nor did the sequencing of Ki-ras reveal mutations. These results are in contrast to most findings in comparable rat studies. The deviations may be due to differences in exposure to the carcinogen or difference in strain and/or age. The lack of -catenin and Ki-ras alterations in this colon cancer model is unlike human sporadic colorectal cancers where these genetic changes are common findings.

Document Type: Research Article

Affiliations: 1: Biomedical Laboratory, Faculty of Health Sciences, University of Southern Denmark, Winsloewparken 23, DK-5000 Odense, Denmark 2: Department of Laboratory Animal Science, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 2, P.O. Box 80166, 3508 TD Utrecht, The Netherlands 3: Department of Pathology, Faculty of Health Sciences, University of Southern Denmark, Winsloewparken 15, DK-5000 Odense Denmark 4: Department of Biochemistry and Molecular Biology, Faculty of Science and Engineering, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark

Publication date: December 1, 2003

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  • Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.

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