{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T07:53:34Z","timestamp":1789890814386,"version":"4.0.1"},"reference-count":53,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,12,19]],"date-time":"2017-12-19T00:00:00Z","timestamp":1513641600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005941","name":"Dietmar Hopp Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005941","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["STR 1160\/1\u20102"],"award-info":[{"award-number":["STR 1160\/1\u20102"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>One mechanism by which alcoholic liver disease (ALD) progresses is oxidative stress and the generation of reactive oxygen species, among others due to the induction of cytochrome P\u20104502E1 (CYP2E1). Experimental data underline the key role of CYP2E1 because ALD could be partially prevented in rats by the administration of the specific CYP2E1 inhibitor chlormethiazole. As CYP2E1 is linked to the formation of carcinogenic etheno DNA adducts in ALD patients, a causal role of alcohol\u2010induced CYP2E1 in hepatocarcinogenesis is implicated. The purpose of this study was to investigate CYP2E1 induction in ALD, and its correlation with oxidative DNA lesions and with hepatic histology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Hepatic biopsies from 97 patients diagnosed with ALD were histologically scored for steatosis, inflammation, and fibrosis. CYP2E1 and the exocyclic etheno DNA adduct 1,N<jats:sup>6<\/jats:sup>\u2010etheno\u20102\u2032deoxyadenosine (\u03b5dA) were determined immunohistochemically. In addition, in 42 patients, 8\u2010hydroxydeoxyguanosine (8\u2010OHdG) was also evaluated using immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A significant positive correlation was found between CYP2E1 and \u03b5dA (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.0001) as well as between CYP2E1 and 8\u2010OHdG (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.039). Both CYP2E1 (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.0094) and \u025bdA (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.0001) also correlated significantly with the stage of hepatic fibrosis. Furthermore, a significant correlation between the fibrosis stage and the grade of lobular inflammation (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.0001) was observed. However, the amount of alcohol consumed did not correlate with any of the parameters determined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data suggest an important role of CYP2E1 in the generation of \u03b5dA, in the fibrotic progression of ALD, and thus in alcohol\u2010mediated hepatocarcinogenesis. CYP2E1 may be a target in the treatment of ALD and a potential prognostic marker for disease progression.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.13546","type":"journal-article","created":{"date-parts":[[2017,11,9]],"date-time":"2017-11-09T13:58:34Z","timestamp":1510235914000},"page":"252-259","source":"Crossref","is-referenced-by-count":46,"title":["Carcinogenic Etheno DNA Adducts in Alcoholic Liver Disease: Correlation with Cytochrome P\u20104502E1 and Fibrosis"],"prefix":"10.1111","volume":"42","author":[{"given":"Sebastian","family":"Mueller","sequence":"first","affiliation":[{"name":"Centre of Alcohol Research University of Heidelberg Heidelberg Germany"},{"name":"Department of Medicine (Gastroenterology &amp; Hepatology) Salem Medical Centre Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Peccerella","sequence":"additional","affiliation":[{"name":"Centre of Alcohol Research University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Qin","sequence":"additional","affiliation":[{"name":"Centre of Alcohol Research University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Glassen","sequence":"additional","affiliation":[{"name":"Centre of Alcohol Research University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00fcdiger","family":"Waldherr","sequence":"additional","affiliation":[{"name":"Centre of Alcohol Research University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christa","family":"Flechtenmacher","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate K.","family":"Straub","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Heidelberg Heidelberg Germany"},{"name":"Institute of Pathology University Medicine University of Mainz Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunda","family":"Millonig","sequence":"additional","affiliation":[{"name":"Centre of Alcohol Research University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Stickel","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology University Hospital Z\u00fcrich Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Bruckner","sequence":"additional","affiliation":[{"name":"Institute of Medical Biometry and Informatics University of Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Bartsch","sequence":"additional","affiliation":[{"name":"Division of Toxicology and Cancer Risk Factors German Cancer Research Centre (DKFZ) Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9467-5815","authenticated-orcid":false,"given":"Helmut Karl","family":"Seitz","sequence":"additional","affiliation":[{"name":"Centre of Alcohol Research University of Heidelberg Heidelberg Germany"},{"name":"Department of Medicine (Gastroenterology &amp; Hepatology) Salem Medical Centre Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,12,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(01)00773-0"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1383-5742(00)00014-4"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3109\/03602539409029802"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00210a031"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20532"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2008.10.020"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3945\/jn.110.136531"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.22.9974"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21375"},{"issue":"1","key":"e_1_2_8_11_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/j.1360-0443.2010.03335.x","article-title":"Identifying the gap between need and intervention for alcohol use disorders in Europe","volume":"106","author":"Drummond C","year":"2011","journal-title":"Addiction"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.04.004"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/10.1.209"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx00044a013"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgh089"},{"key":"e_1_2_8_16_1","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/978-94-007-5881-0_4","volume-title":"Cytochrome P\u20104502E1: Its Role in Disease and Drug Metabolism","author":"French SW","year":"2013"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510260423"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-1373.2000.22435.x"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/23.11.1781"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20701"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.08.018"},{"key":"e_1_2_8_22_1","first-page":"4098","article-title":"Mutagenesis induced by a single 1, N6\u2010ethenodeoxyadenosine adduct in human cells","volume":"60","author":"Levine RL","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_8_23_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.hepres.2003.08.001","article-title":"CYP2E1: from ASH to NASH","volume":"28","author":"Lieber CS","year":"2003","journal-title":"Hepatol Res"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2014.08.009"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21241"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2010.07.026"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22222"},{"key":"e_1_2_8_28_1","doi-asserted-by":"crossref","first-page":"41464","DOI":"10.18632\/oncotarget.6203","article-title":"Identification of cytochrome P\u20104502E1 as a critical mediator of alcohol effects on steatotic hepatocytes","volume":"8","author":"Mahli A","year":"2015","journal-title":"Oncotarget"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1983.151"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.25604"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.33720"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110506200"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.30362"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(01)00223-9"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi960170h"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(90)90153-A"},{"key":"e_1_2_8_37_1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/nature03688","article-title":"Rac1b and reactive oxygen species mediate MMP\u20103\u2010induced EMT and genomic instability","volume":"436","author":"Rodisky DC","year":"2005","journal-title":"Nature"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2191"},{"key":"e_1_2_8_39_1","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/978-94-007-5881-0_3","volume-title":"Cytochrome P\u20104502E1: Its Role in Disease and Drug Metabolism","author":"Seitz HK","year":"2013"},{"key":"e_1_2_8_40_1","first-page":"320","article-title":"1, N2\u2010ethenodeoxyguanosine as a potential marker for DNA adduct formation by trans\u20104\u2010hydroxy\u20102\u2010nonenal","volume":"48","author":"Sodum RS","year":"1988","journal-title":"Cancer Res"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx00007a004"},{"key":"e_1_2_8_42_1","first-page":"137","article-title":"Stereoselective formation of in\u00a0vitro nucleic acid adducts by 2,3\u2010epoxy\u20104\u2010hydroxynonanal","volume":"51","author":"Sodum RS","year":"1991","journal-title":"Cancer Res"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/13.4.727"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-013-2574-4"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840100407"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1110(88)90022-X"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22978"},{"key":"e_1_2_8_48_1","first-page":"5682","article-title":"Formation of cyclic adducts of deoxyguanosine with the aldehydes trans\u20104\u2010hydroxy\u20102\u2010hexenal and trans\u20104\u2010hydroxy 2\u2010nonenal in\u00a0vitro","volume":"46","author":"Winter CK","year":"1986","journal-title":"Cancer Res"},{"key":"e_1_2_8_49_1","unstructured":"2009 World Health Organization Geneva World Health Organization Global Health Risks: Mortality and Burden of Disease Related to Selected Major Risks"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22087"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/21.4.777"},{"key":"e_1_2_8_52_1","first-page":"683","article-title":"Immunoperoxidase detection of 8\u2010hydroxydeoxyguanosine in aflatoxin B1\u2010treated rat liver and human oral mucosal cells","volume":"15","author":"Yarborough A","year":"1996","journal-title":"Cancer Res"},{"key":"e_1_2_8_53_1","first-page":"5","article-title":"Cytochrome P4502E1 inhibition prevents hepatic carcinogenesis induced by diethylnitrosamine in alcohol fed rats","volume":"1","author":"Ye Q","year":"2012","journal-title":"Hepatobiliary Surg Nutr"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25670"}],"container-title":["Alcoholism: Clinical and Experimental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Facer.13546","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acer.13546","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T20:29:15Z","timestamp":1695846555000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acer.13546"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,19]]},"references-count":53,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,2]]}},"alternative-id":["10.1111\/acer.13546"],"URL":"https:\/\/doi.org\/10.1111\/acer.13546","archive":["Portico"],"relation":{},"ISSN":["0145-6008","1530-0277"],"issn-type":[{"value":"0145-6008","type":"print"},{"value":"1530-0277","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,19]]}}}