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dc.contributor.advisorLeona D. Samson.en_US
dc.contributor.authorGreen, Stephanie Laurenen_US
dc.contributor.otherMassachusetts Institute of Technology. Biological Engineering Division.en_US
dc.date.accessioned2006-09-28T15:12:51Z
dc.date.available2006-09-28T15:12:51Z
dc.date.copyright2006en_US
dc.date.issued2006en_US
dc.identifier.urihttp://hdl.handle.net/1721.1/34157
dc.descriptionThesis (S.M.)--Massachusetts Institute of Technology, Biological Engineering Division, 2006.en_US
dc.descriptionIncludes bibliographical references (leaves 92-93).en_US
dc.description.abstractThe two most common forms of inflammatory bowel disease (IBD) are ulcerative colitis (UC) and Crohn's Disease (CD), which affect more than 1 million Americans. Recently the incidence of IBD has been rising in Japan, Europe and North America.' Colorectal cancer is a very serious complication of IBD, and a patient's risk increases with increasing extent and duration of disease.2 There is no cure for CD, and the only cure for UC is removal of the entire colon and rectum. It is thought that cancer risk is based on chronic inflammation of the gastrointestinal mucosa. There have been many studies, which have supported this idea and have made progress toward understanding the link between chronic inflammation and cancer. In both UC and CD, it is known that there are increased levels of EA, cG, and eC, which are potentially miscoding lesions, in the DNA of affected tissues.3 Also, 3-methyladenine DNA glycosylase (Aag in mice), an initiator of the Base Excision Repair pathway, shows adaptively increasing activity in response to increased inflammation in UC colon epithelium.4 This thesis demonstrates the importance of Aag in protecting against the effects of chronic inflammation.en_US
dc.description.abstract(cont.) It was found that Aag deficient mice, treated with 5 cycles of dextran sulfate sodium (DSS) to induce chronic inflammation, showed significant signs of increased disease including decreased colon length, increased spleen weight, and increase in epithelial defects. Also, when treated with a tumor initiator, azoxymethane, prior to DSS exposure, Aag deficient mice show a 2.95 fold (p<0.0001) increase in tumor multiplicity compared to wild type treated animals, as well as decreased colon length, increased spleen weight, increased dysplasia/neoplasia, and increased area affected by dysplasia/neoplasia. If UC patients had a deficiency in 3-methyladenine-DNA-glycosylase activity, they would likely be more susceptible to mutations and cancer because of their inability to repair DNA damage caused by inflammatory cytokines and reactive oxygen and nitrogen species. In future studies, it would be beneficial to determine if transgenic Aag over-expresser mice show protection against the damage induced by chronic inflammation. This would make intestinal gene therapy a possible approach to finding the first cure for IBD and inflammation associated colorectal cancer.en_US
dc.description.statementofresponsibilityby Stephanie Lauren Green.en_US
dc.format.extent93 leavesen_US
dc.format.extent4988471 bytes
dc.format.extent4992321 bytes
dc.format.mimetypeapplication/pdf
dc.format.mimetypeapplication/pdf
dc.language.isoengen_US
dc.publisherMassachusetts Institute of Technologyen_US
dc.rightsMIT theses may be protected by copyright. Please reuse MIT thesis content according to the MIT Libraries Permissions Policy, which is available through the URL provided.en_US
dc.rights.urihttp://dspace.mit.edu/handle/1721.1/7582
dc.subjectBiological Engineering Division.en_US
dc.titleDNA alkylation repair deficient mice are susceptible to chemically induced Inflammatory Bowel Diseaseen_US
dc.title.alternativeDeoxyribonucleic acid alkylation repair deficient mice are susceptible to chemically induced IBDen_US
dc.typeThesisen_US
dc.description.degreeS.M.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineering
dc.identifier.oclc69019092en_US


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