{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T20:32:06Z","timestamp":1774038726385,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2012,9,17]],"date-time":"2012-09-17T00:00:00Z","timestamp":1347840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recently, chronic Aristolochia poisoning was found responsible for the aetiology of Balkan endemic nephropathy (BEN) in Croatia, Serbia, and Bosnia, and diet was the likely route of exposure to aristolochic acid (AA). BEN, often associated with an increased incidence of upper urinary tract carcinoma (UUC), also affects residents of certain rural villages in Romania. AA is a nephrotoxin and human carcinogen that forms DNA adducts after metabolic activation, which induce characteristic <jats:italic>TP53<\/jats:italic> mutations in urothelial tumours. Here we present the first evidence linking AA exposure to UUC in residents of an endemic region in the Romanian Mehedinti County. DNA was extracted from kidney and tumour tissue of seven patients who underwent nephroureterectomy for UUC and resided in BEN villages (endemic group). Five patients with UUC from nonendemic villages served as controls. AA\u2010DNA adducts (7\u2010(deoxyadenosin\u2010<jats:italic>N<\/jats:italic><jats:sup>6<\/jats:sup>\u2010yl)\u2010aristolactam I), established biomarkers of AA exposure, were identified by <jats:sup>32<\/jats:sup>P\u2010postlabelling in renal DNA of six patients from the endemic group and in one of the nonendemic group (adduct levels ranged from 0.3 to 6.5 adducts per 10<jats:sup>8<\/jats:sup> nucleotides). Additionally, an A to T transversion in <jats:italic>TP53<\/jats:italic>, a base substitution characteristic of AA mutagenic activity was found in urothelial tumour DNA of one patient from the endemic group. Our results provide a molecular link to the cause of urothelial tumours in BEN regions of Romania indicating that AA is the common aetiological agent for BEN across its numerous geographical foci. Environ. Mol. Mutagen., 2012. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/em.21732","type":"journal-article","created":{"date-parts":[[2012,9,17]],"date-time":"2012-09-17T08:59:07Z","timestamp":1347872347000},"page":"636-641","source":"Crossref","is-referenced-by-count":53,"title":["Evidence of exposure to aristolochic acid in patients with urothelial cancer from a Balkan endemic nephropathy region of Romania"],"prefix":"10.1002","volume":"53","author":[{"given":"Heinz H.","family":"Schmeiser","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jill E.","family":"Kucab","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Volker M.","family":"Arlt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David H.","family":"Phillips","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Hollstein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gheorghe","family":"Gluhovschi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Gluhovschi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirela","family":"Modilca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liviu","family":"Daminescu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ligia","family":"Petrica","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Velciov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,9,17]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.10602"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgm082"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/18.5.1063"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1119920109"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002040050568"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2008.129"},{"key":"e_1_2_6_8_1","first-page":"34","article-title":"Fifty years of Balkan endemic nephropathy in Romania: Some aspects of the endemic focus in the Mehedinti county","volume":"75","author":"Gluhovschi G","year":"2011","journal-title":"Clin Nephrol"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0701248104"},{"key":"e_1_2_6_10_1","first-page":"116","article-title":"Endemic nephropathy: the case for chronic poisoning by aristolochia","volume":"46","author":"Hranjec T","year":"2005","journal-title":"Croat Med J"},{"key":"e_1_2_6_11_1","first-page":"347","volume-title":"Plants Containing Aristolochic Acid. 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