{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:18:04Z","timestamp":1790144284696,"version":"4.0.1"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2004,6,4]],"date-time":"2004-06-04T00:00:00Z","timestamp":1086307200000},"content-version":"vor","delay-in-days":155,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[2004,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nitric oxide (NO<jats:sup>\u00b7<\/jats:sup>), which is generated under chronic inflammatory conditions that predispose individuals to cancer, has paradoxical effects. NO<jats:sup>\u00b7<\/jats:sup> can activate p53, which can result in anti\u2010carcinogenic effects, or it can be mutagenic and increase cancer risk. We explored the mechanisms by which NO<jats:sup>\u00b7<\/jats:sup> induced p53 activation in vitro and found that NO<jats:sup>\u00b7<\/jats:sup> induced p53 accumulation and phosphorylation, particularly at ser\u201015, via ATM and ATR kinases, which then led to cell cycle arrest at G<jats:sub>2<\/jats:sub>\/M. We next examined proteins in these pathways in both inflamed and normal human colon tissue. Inducible nitric oxide synthase (iNOS) levels and p53\u2010P\u2010ser15 levels were positively correlated with the degree of inflammation and with each other. Additionally, the p53 targets, HDM\u20102 and p21 (WAF1), were present in ulcerative colitis (UC) colon, but undetectable in normal colon, consistent with activated p53. We also found higher <jats:italic>p53<\/jats:italic> mutant frequencies of both G:C \u2192 A:T transitions at the CpG site of codon 248 and C:G \u2192 T:A transitions at codon 247 in lesional colon tissue from UC cases versus nonlesional tissue from these cases or colon tissue from normal adult controls. Consistent with nitrosative stress and the deamination of 5\u2010methylcytosine, <jats:italic>p53<\/jats:italic> mutations were also detected in sporadic colon cancer tissue and were associated with iNOS activity in these tissues. These studies identified a potential mechanistic link between NO<jats:sup>\u00b7<\/jats:sup> and p53 in UC and sporadic colon cancer. Environ. Mol. Mutagen. 44:3\u20139, 2004. Published 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/em.20024","type":"journal-article","created":{"date-parts":[[2004,6,7]],"date-time":"2004-06-07T07:01:16Z","timestamp":1086591676000},"page":"3-9","source":"Crossref","is-referenced-by-count":80,"title":["Nitric oxide and p53 in cancer\u2010prone chronic inflammation and oxyradical overload disease"],"prefix":"10.1002","volume":"44","author":[{"given":"Julie E.","family":"Goodman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorne J.","family":"Hofseth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Perwez","family":"Hussain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Curtis C.","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,6,4]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.11.6.9194524"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/91.1.86"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.12.5258"},{"key":"e_1_2_1_5_1","first-page":"227","article-title":"Signaling to p53: breaking the posttranslational modification code","volume":"48","author":"Appella E","year":"2000","journal-title":"Pathol Biol (Paris)"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(97)80013-3"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(95)90291-0"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19880515)61:10<1942::AID-CNCR2820611003>3.0.CO;2-J"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400582"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(92)91184-6"},{"key":"e_1_2_1_11_1","first-page":"123","article-title":"Molecular genetic studies of the adenoma\u2010carcinoma sequence","volume":"39","author":"Fearon ER","year":"1994","journal-title":"Adv Intern Med"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.6.2442"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.35.11.1590"},{"key":"e_1_2_1_14_1","first-page":"4855","article-title":"Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis","volume":"54","author":"Greenblatt MS","year":"1994","journal-title":"Cancer Res"},{"key":"e_1_2_1_15_1","first-page":"1","article-title":"Solving the viral\u2010chemical puzzle of human liver carcinogenesis","volume":"3","author":"Harris CC","year":"1994","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0237083100"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1905840"},{"key":"e_1_2_1_18_1","first-page":"3333","article-title":"Increased p53 mutation load in noncancerous colon tissue from ulcerative colitis: a cancer\u2010prone chronic inflammatory disease","volume":"60","author":"Hussain SP","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1046"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.10.4392"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202862200"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/351453a0"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65415-6"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3190299"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204100"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-9861(03)00283-2"},{"key":"e_1_2_1_27_1","first-page":"179","article-title":"The comet assay. An overview of techniques","volume":"203","author":"Olive PL","year":"2002","journal-title":"Methods Mol Biol"},{"key":"e_1_2_1_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng989"},{"key":"e_1_2_1_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.36.5.718"},{"key":"e_1_2_1_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(83)80175-0"},{"key":"e_1_2_1_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205563"},{"key":"e_1_2_1_32_1","first-page":"1929","article-title":"Inflammation, chromosomal instability, and cancer: the schistosomiasis model","volume":"54","author":"Rosin MP","year":"1994","journal-title":"Cancer Res"},{"key":"e_1_2_1_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(96)70055-0"},{"key":"e_1_2_1_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx9600311"},{"key":"e_1_2_1_35_1","first-page":"2035","article-title":"Adenomatous polyposis coli gene mutations in ulcerative colitis\u2010associated dysplasias and cancers versus sporadic colon neoplasms","volume":"55","author":"Tarmin L","year":"1995","journal-title":"Cancer Res"},{"key":"e_1_2_1_36_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198809013190901"},{"key":"e_1_2_1_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellbi.2006.11.012"},{"key":"e_1_2_1_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1201-e277"},{"key":"e_1_2_1_39_1","doi-asserted-by":"publisher","DOI":"10.1159\/000064540"},{"key":"e_1_2_1_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0070-2137(96)80006-9"},{"key":"e_1_2_1_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/35010529"},{"key":"e_1_2_1_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(93)90639-T"},{"key":"e_1_2_1_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(02)00866-3"}],"container-title":["Environmental and Molecular Mutagenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fem.20024","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/em.20024","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T19:05:17Z","timestamp":1696619117000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/em.20024"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,1]]},"references-count":42,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2004,1]]}},"alternative-id":["10.1002\/em.20024"],"URL":"https:\/\/doi.org\/10.1002\/em.20024","archive":["Portico"],"relation":{},"ISSN":["0893-6692","1098-2280"],"issn-type":[{"value":"0893-6692","type":"print"},{"value":"1098-2280","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,1]]}}}