{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T15:47:34Z","timestamp":1783525654262,"version":"3.55.0"},"reference-count":74,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2010,2,1]],"date-time":"2010-02-01T00:00:00Z","timestamp":1264982400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxicol Pathol"],"published-print":{"date-parts":[[2010,2]]},"abstract":"<jats:p>Furan is a potent cholangiocarcinogen in rat by an as yet undefined mechanism. The risk to man remains unclear. Using a time-course stop study design, we have investigated the potential of furan to induce oxidative stress and DNA damage associated with inflammatory and regenerative responses in rat liver. Furan was administered via oral gavage (30\u2009mg\/kg b.w. 5 daily doses per week), and livers were analyzed at time points between eight hr and three months. A one-month recovery group previously treated for three months was also included. There was a marked association between CYP2E1 expression and DNA oxidation (8-oxo-dG) in areas of centrilobular hepatocyte necrosis seen after a single dose. After one-month recovery from three-month treatment, 8-oxo-dG was still observed in areas of furan-induced cholangiofibrosis. Furan-induced changes in the expression of various genes associated with oxidative stress, DNA damage, and cell cycle control were identified during treatment and recovery. We propose that furan-induced cholangiocarcinomas emerge from areas of cholangiofibrosis as a result of a combination of chronic, persistent indirect damage to DNA through oxygen radicals coupled with persistent proliferative signals, including loss of connexin 32, that act to convert this DNA damage to fixed mutations.<\/jats:p>","DOI":"10.1177\/0192623309357946","type":"journal-article","created":{"date-parts":[[2010,2,2]],"date-time":"2010-02-02T23:14:32Z","timestamp":1265152472000},"page":"230-243","source":"Crossref","is-referenced-by-count":61,"title":["Evidence of Oxidative Stress and Associated DNA Damage, Increased Proliferative Drive, and Altered Gene Expression in Rat Liver Produced by the Cholangiocarcinogenic Agent Furan"],"prefix":"10.1177","volume":"38","author":[{"given":"K. C.","family":"Hickling","sequence":"first","affiliation":[{"name":"Safety Assessment, AstraZeneca R&D Charnwood, Loughborough, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. M.","family":"Hitchcock","sequence":"additional","affiliation":[{"name":"Molecular Toxicology Drug Safety Research & Development Pfizer Ltd Sandwich, Kent, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Oreffo","sequence":"additional","affiliation":[{"name":"Safety Assessment, AstraZeneca R&D Charnwood, Loughborough, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Mally","sequence":"additional","affiliation":[{"name":"Department of Toxicology, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. G.","family":"Hammond","sequence":"additional","affiliation":[{"name":"Safety Assessment, AstraZeneca R&D Charnwood, Loughborough, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. G.","family":"Evans","sequence":"additional","affiliation":[{"name":"Safety Assessment, AstraZeneca R&D Charnwood, Loughborough, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. K.","family":"Chipman","sequence":"additional","affiliation":[{"name":"School of Biosciences, The University of Birmingham, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2010,2,2]]},"reference":[{"key":"bibr1-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.1999.00654.x"},{"key":"bibr2-0192623309357946","first-page":"2555","volume":"36","author":"Bannasch P.","year":"1976","journal-title":"Cancer Research"},{"key":"bibr3-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2004.10.025"},{"key":"bibr4-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1080\/15287399109531564"},{"key":"bibr5-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1002\/mc.2940090106"},{"key":"bibr6-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1021\/tx0101402"},{"key":"bibr7-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1021\/tx049866z"},{"key":"bibr8-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1006\/taap.1993.1245"},{"key":"bibr9-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/10.suppl_4.S308"},{"key":"bibr10-0192623309357946","first-page":"707","volume":"147","author":"Chen J. R.","year":"1995","journal-title":"Am J Pathol"},{"key":"bibr11-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(87)90021-2"},{"key":"bibr12-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1016\/S108495210200126X"},{"key":"bibr13-0192623309357946","first-page":"5752","volume":"51","author":"Elmore L. W.","year":"1991","journal-title":"Cancer Res"},{"key":"bibr14-0192623309357946","first-page":"1220","volume":"16","author":"Elmore L. W.","year":"1992","journal-title":"Hepatology"},{"key":"bibr15-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-483X(97)03618-4"},{"key":"bibr16-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2559.1999.00705.x"},{"key":"bibr17-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrgentox.2004.11.005"},{"key":"bibr18-0192623309357946","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1016\/0270-9139(95)90071-3","volume":"21","author":"Grasl-Kraupp B.","year":"1995","journal-title":"Hepatology"},{"key":"bibr19-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1039\/b415092a"},{"key":"bibr20-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2003.12.021"},{"key":"bibr21-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1177\/0192623309357945"},{"key":"bibr22-0192623309357946","first-page":"71","volume":"192","author":"Hitchcock J. M.","year":"2003","journal-title":"Toxicology"},{"key":"bibr23-0192623309357946","volume":"66","author":"Hitchcock J. M.","year":"2002","journal-title":"Toxicologist"},{"key":"bibr24-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/10.suppl_4.S122"},{"key":"bibr25-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2003.12.020"},{"key":"bibr26-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1827.1999.00821.x"},{"key":"bibr27-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2744(199704)18:4<199::AID-MC3>3.0.CO;2-9"},{"key":"bibr28-0192623309357946","first-page":"477","volume":"79","author":"Kang Y. K.","year":"1999","journal-title":"Lab Invest"},{"key":"bibr29-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrgentox.2008.08.014"},{"key":"bibr30-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(02)00297-0"},{"key":"bibr31-0192623309357946","first-page":"59","volume":"38","author":"Kuszyk B. S.","year":"1997","journal-title":"Critic Rev Diagn Imaging"},{"key":"bibr32-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2000.8108"},{"key":"bibr33-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1218(94)90072-8"},{"key":"bibr34-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1080\/10408397909527268"},{"key":"bibr35-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-483X(02)00393-1"},{"key":"bibr36-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201138"},{"key":"bibr37-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1177\/019262339101900401"},{"key":"bibr38-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1002\/em.2860120111"},{"key":"bibr39-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2744(199710)20:2<194::AID-MC6>3.0.CO;2-N"},{"key":"bibr40-0192623309357946","first-page":"421","volume-title":"Theory and Practice of Histological Techniques","author":"Miller K. D.","year":"2002"},{"key":"bibr41-0192623309357946","first-page":"1","volume":"402","author":"National Toxicology Program","year":"1993","journal-title":"Natl Toxicol Program Tech Rep Ser"},{"key":"bibr42-0192623309357946","first-page":"130","volume":"10","author":"National Toxicology Program","year":"2002","journal-title":"Carcinogen Profiles"},{"key":"bibr43-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204248"},{"key":"bibr44-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21466"},{"key":"bibr45-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(99)80036-2"},{"key":"bibr46-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202821"},{"key":"bibr47-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-230X(02)84004-0"},{"key":"bibr48-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20178"},{"key":"bibr49-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64082-5"},{"key":"bibr50-0192623309357946","first-page":"537","volume":"2","author":"Parkin D. M.","year":"1993","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"bibr51-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.2570080103"},{"key":"bibr52-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1021\/jf0490403"},{"key":"bibr53-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1021\/tx000065f"},{"key":"bibr54-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510290524"},{"key":"bibr55-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64766-9"},{"key":"bibr56-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1080\/004982599238317"},{"key":"bibr57-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65178-4"},{"key":"bibr58-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1136\/gut.49.4.565"},{"key":"bibr59-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204383"},{"key":"bibr60-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.8004"},{"key":"bibr61-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1177\/019262339602400113"},{"key":"bibr62-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510260241"},{"key":"bibr63-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1007\/BF01298882"},{"key":"bibr64-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1746.2001.02438.x"},{"key":"bibr65-0192623309357946","first-page":"1685","volume":"151","author":"Sirica A. E.","year":"1997","journal-title":"Am J Pathol"},{"key":"bibr66-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2184.1994.tb01490.x"},{"key":"bibr67-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1136\/gut.47.5.721"},{"key":"bibr68-0192623309357946","first-page":"418","volume":"114","author":"Tatematsu M.","year":"1984","journal-title":"Am J Pathol"},{"key":"bibr69-0192623309357946","first-page":"354","volume":"52","author":"Tatematsu M.","year":"1985","journal-title":"Lab Invest"},{"key":"bibr70-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1136\/gut.48.6.816"},{"key":"bibr71-0192623309357946","first-page":"306","volume":"5","author":"Thuluvath P. J.","year":"1997","journal-title":"Gastroenterologist"},{"key":"bibr72-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200197200"},{"key":"bibr73-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1002\/em.2850190305"},{"key":"bibr74-0192623309357946","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2559.2003.01728.x"}],"container-title":["Toxicologic Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0192623309357946","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0192623309357946","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0192623309357946","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T16:31:29Z","timestamp":1777653089000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0192623309357946"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,2]]},"references-count":74,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2010,2]]}},"alternative-id":["10.1177\/0192623309357946"],"URL":"https:\/\/doi.org\/10.1177\/0192623309357946","relation":{},"ISSN":["0192-6233","1533-1601"],"issn-type":[{"value":"0192-6233","type":"print"},{"value":"1533-1601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,2]]}}}