This is a multidisciplinary and multicenter approach to the study of naturally occurring colitis and colon cancer in the cotton-top tamarin (CTT) Saguinus oedipus. Collaborative studies will be carried out by investigators of the New England Regional Primate Center, Children's Hospital Medical Center (Boston) and the Massachusetts General Hospital. Major areas of investigation include the following: 1) Characterization of the spontaneously occurring chronic colitis in CTT and its relevance to human colitis: The natural history of colitis and cancer, including age of onset, prevalence and clinical manifestations will be delineated by a broad based approach involving a variety of clinical, histologic, radiologic and endoscopic studies. The role of dietary, environmental and genetic factors will be assessed as well as the potential efficacy of a variety of anti-inflammatory agents (Project 1). 2) Assessment of the role of immunologic changes and immunoregulatory dysfunction in the pathogenesis of CTT colitis: Studies will be directed both to the characterization of basic immune mechanisms in the CTT (Project 3) as well as determination of immune alterations in relationship to the development of colitis (Project 2). The latter efforts will encompass studies on peripheral lymphocytes, intestinal T cells and evaluation of the potential role of colonic antigen(s) in the perpetuation of chronic mucosal inflammation. 3) Evaluation of colonic glycoprotein structure and metabolism in the CTT and their relationship to colitis and colon cancer: The structure, as well as biosynthetic and degradative pathways of colonic glycoproteins will be studied by a variety of methods. Particular attention will be directed to delineation of the biochemical basis of a selective reduction in a specific colonic mucin glycoprotein (mucin species IV) found in both CTT and patients with ulcerative colitis. 4) Delineation of molecular mechanisms of malignant transformation in the CTT: Molecular biologic techniques will be used to define the potential role of specific oncogenes and/or endogenous retroviral sequences in the evolution of colonic cancer in the CTT. Studies utilizing tissue samples, isolated cell suspensions and primary and established cell lines will assess molecular mechanisms involved in the progression from chronic colitis to colon cancer including potential structural and functional changes in transforming or endogenous retroviral genetic sequences.
