{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T22:14:47Z","timestamp":1766268887471},"reference-count":49,"publisher":"American Association for Cancer Research (AACR)","issue":"5","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The role of ataxia telangiectasia mutated (ATM), a DNA double-strand break recognition and response protein, in inflammation and inflammatory diseases is unclear. We have previously shown that high levels of systemic DNA damage are induced by intestinal inflammation in wild-type mice. To determine the effect of Atm deficiency in inflammation, we induced experimental colitis in Atm\u2212\/\u2212, Atm+\/\u2212, and wild-type mice via dextran sulfate sodium (DSS) administration. Atm\u2212\/\u2212 mice had higher disease activity indices and rates of mortality compared with heterozygous and wild-type mice. Systemic DNA damage and immune response were characterized in peripheral blood throughout and after three cycles of treatment. Atm\u2212\/\u2212 mice showed increased sensitivity to levels of DNA strand breaks in peripheral leukocytes, as well as micronucleus formation in erythroblasts, compared with heterozygous and wild-type mice, especially during remission periods and after the end of treatment. Markers of reactive oxygen and nitrogen species\u2013mediated damage, including 8-oxoguanine and nitrotyrosine, were present both in the distal colon and in peripheral leukocytes, with Atm\u2212\/\u2212 mice manifesting more 8-oxoguanine formation than wild-type mice. Atm\u2212\/\u2212 mice showed greater upregulation of inflammatory cytokines and significantly higher percentages of activated CD69+ and CD44+ T cells in the peripheral blood throughout treatment. ATM, therefore, may be a critical immunoregulatory factor dampening the deleterious effects of chronic DSS-induced inflammation, necessary for systemic genomic stability and homeostasis of the gut epithelial barrier. Cancer Res; 70(5); 1875\u201384<\/jats:p>","DOI":"10.1158\/0008-5472.can-09-2584","type":"journal-article","created":{"date-parts":[[2010,2,24]],"date-time":"2010-02-24T03:05:16Z","timestamp":1266980716000},"page":"1875-1884","update-policy":"http:\/\/dx.doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["<i>Atm<\/i>-Deficient Mice Exhibit Increased Sensitivity to Dextran Sulfate Sodium\u2013Induced Colitis Characterized by Elevated DNA Damage and Persistent Immune Activation"],"prefix":"10.1158","volume":"70","author":[{"given":"Aya M.","family":"Westbrook","sequence":"first","affiliation":[{"name":"Authors' Affiliations:\u20081Department of Pathology and Laboratory Medicine, 2Molecular Toxicology Interdepartmental Program, and 3Department of Radiation Oncology, University of California at Los Angeles School of Medicine, Los Angeles, California"}]},{"given":"Robert H.","family":"Schiestl","sequence":"additional","affiliation":[{"name":"Authors' Affiliations:\u20081Department of Pathology and Laboratory Medicine, 2Molecular Toxicology Interdepartmental Program, and 3Department of Radiation Oncology, University of California at Los Angeles School of Medicine, Los Angeles, California"},{"name":"Authors' Affiliations:\u20081Department of Pathology and Laboratory Medicine, 2Molecular Toxicology Interdepartmental Program, and 3Department of Radiation Oncology, University of California at Los Angeles School of Medicine, Los Angeles, California"},{"name":"Authors' Affiliations:\u20081Department of Pathology and Laboratory Medicine, 2Molecular Toxicology Interdepartmental Program, and 3Department of Radiation Oncology, University of California at Los Angeles School of Medicine, Los Angeles, 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