{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:15:18Z","timestamp":1788869718614,"version":"build-2803163510"},"reference-count":55,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2010,12,6]],"date-time":"2010-12-06T00:00:00Z","timestamp":1291593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SCHU 2367\/1\u20131"],"award-info":[{"award-number":["SCHU 2367\/1\u20131"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2011,3]]},"abstract":"<jats:p>\n                    Epidemiological studies exploring the connection between hypertension and cancer demonstrate a higher cancer incidence, especially of kidney cancer, and a higher cancer mortality in hypertensive patients. Hormones elevated in hypertension,\n                    <jats:italic>i.e.,<\/jats:italic>\n                    aldosterone and angiotensin II, which exert genotoxic effects\n                    <jats:italic>in vitro,<\/jats:italic>\n                    could contribute to carcinogenesis in hypertension. The present study was conducted to investigate the possible DNA\u2010damaging effect of aldosterone receptor activation\n                    <jats:italic>in vivo.<\/jats:italic>\n                    Crl:CD (Sprague\u2010Dawley) rats were treated for 6 wk with desoxycorticosterone acetate (DOCA) and salt to induce a mineralocorticoid\u2010dependent hypertension. DOCA\u2010salt treatment caused increased blood pressure (+26 mmHg) compared to untreated rats, elevated markers of kidney failure (up to 62\u2010fold for Kim\u20101), and the induction of several proinflammatory genes and proteins (up to 2.6\u2010fold for tissue MCP\u20101). The mineralocorticoid receptor (MR) antagonist spironolactone (MR IC\n                    <jats:sub>50<\/jats:sub>\n                    24 nM) and the novel nonsteroidal antagonist BR\u20104628 (MR IC\n                    <jats:sub>50<\/jats:sub>\n                    28 nM) decreased these damage markers. DOCA\u2010salt treatment also caused 8.8\u2010fold increased structural DNA damage, determined with the comet assay, double\u2010strand breaks (3.5\u2010fold), detected immunohistochemically, and oxidative stress. Furthermore, the oxidatively modified mutagenic DNA base 7,8\u2010dihydro\u20108\u2010oxo\u2010guanine (8\u2010oxodG), quantified by LC\u2010MS\/MS, was almost 2\u2010fold higher in DOCA\u2010salt\u2010treated kidneys. Our results suggest a mutagenic potential of high mineralocorticoid levels, frequent in hypertensive individuals.\u2014Schupp, N., Kolkhof, P., Queisser, N., Gartner, S., Schmid, U., Kretschmer, A., Hartmann, E., Oli, R G., Sch\u00e4fer, S., Stopper, H. Mineralocorticoid receptor\u2010mediated DNA damage in kidneys of DOCA\u2010salt hypertensive rats.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    25, 968\u2013978 (2011).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.10-173286","type":"journal-article","created":{"date-parts":[[2010,12,7]],"date-time":"2010-12-07T00:40:42Z","timestamp":1291682442000},"page":"968-978","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Mineralocorticoid receptor\u2010mediated DNA damage in kidneys of DOCA\u2010salt hypertensive rats"],"prefix":"10.1096","volume":"25","author":[{"given":"Nicole","family":"Schupp","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Toxicology University of W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kolkhof","sequence":"additional","affiliation":[{"name":"Cardiology Research Bayer Schering Pharma AG Wuppertal Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Queisser","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology University of W\u00fcrzburg W\u00fcrzburg Germany"},{"name":"Cardiology Research Bayer Schering Pharma AG Wuppertal Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"G\u00e4rtner","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology University of W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Schmid","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology University of W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Kretschmer","sequence":"additional","affiliation":[{"name":"Target Discovery Bayer Schering Pharma AG Wuppertal Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Institute of Toxicology Global Drug Discovery Bayer Schering Pharma AG Wuppertal Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajaraman G.","family":"Oli","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology University of W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Sch\u00e4fer","sequence":"additional","affiliation":[{"name":"Cardiology Research Bayer Schering Pharma AG Wuppertal Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helga","family":"Stopper","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology University of W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,12,6]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.01060306"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2006.07.059"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra000050"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20070123"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909023411001"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2007101079"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.FMJ05003X3"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2006.03.038"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2005.03.007"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2008.02.297"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1243253"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20011101)92:9<2462::AID-CNCR1596>3.0.CO;2-L"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1081\/CNV-200055962"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(02)01049-5"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.2174\/157488607780598296"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-1310"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm306"},{"key":"e_1_2_6_19_1","volume-title":"Image J","author":"Rasband W. 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