{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T10:24:41Z","timestamp":1777717481650,"version":"3.51.4"},"reference-count":37,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2006,1,1]],"date-time":"2006-01-01T00:00:00Z","timestamp":1136073600000},"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":["Int J Toxicol"],"published-print":{"date-parts":[[2006,1]]},"abstract":"<jats:p>\n                    Tumorigenic mechanisms due to chemical exposure are broadly classified as either genotoxic or nongenotoxic. Genotoxic mechanisms are generally well defined; however nongenotoxic modes of tumorgenesis are less straightforward. This study was undertaken to help elucidate dose-response changes in gene expression (transcriptome) in the liver of rats in response to administration of known genotoxic or nongenotoxic liver carcinogens. Male Big Blue Fischer 344 rats were treated for 28-days with 0, 0.1, 0.3, 1.0, or 3.0 mg\/kg\/day of the genotoxin 2-acetylaminofluorene (AAF) or 0, 10, 30, 60, or 100 mg\/kg\/day of the nongenotoxin phenobarbital (PB). Transcriptome analysis was performed using the relatively focused Clontech Rat Toxicology II microarray (465 genes) and hybridized with\n                    <jats:sup>32<\/jats:sup>\n                    P-labeled cDNA target. The analysis indicated that after 28 days of treatment, AAF altered the expression of 14 genes (9 up-and 5 down-regulated) and PB altered the expression of 18 genes (10 up- and 8 down-regulated). Of the limited genes whose expression was altered by AAF and PB, four were altered in common, two up-regulated, and two down-regulated. Several of the genes that show modulation of transcriptional activity following AAF and PB treatment display an atypical dose-response relationship such that the expression at the higher doses tended to be similar to that of control. This high-dose effect could potentially be caused by adaptation, toxicity, or tissue remodeling. These results suggest that the transcriptional response of the cells to higher doses of a toxic agent is likely to be different from that of a low-dose exposure.\n                  <\/jats:p>","DOI":"10.1080\/10915810500488429","type":"journal-article","created":{"date-parts":[[2006,3,1]],"date-time":"2006-03-01T12:35:10Z","timestamp":1141216510000},"page":"57-64","source":"Crossref","is-referenced-by-count":11,"title":["Gene Expression Dose-Response of Liver with a Genotoxic and Nongenotoxic Carcinogen"],"prefix":"10.1177","volume":"25","author":[{"given":"Shawn D.","family":"Seidel","sequence":"first","affiliation":[{"name":"Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William T.","family":"Stott","sequence":"additional","affiliation":[{"name":"Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. Lynn","family":"Kan","sequence":"additional","affiliation":[{"name":"Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barney R.","family":"Sparrow","sequence":"additional","affiliation":[{"name":"Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B. Bhaskar","family":"Gollapudi","sequence":"additional","affiliation":[{"name":"Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2006,1,1]]},"reference":[{"key":"b1-0250057","first-page":"243","volume":"9","author":"Bannasch P","year":"1986","journal-title":"Cancer Detect Prev"},{"key":"b2-0250057","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/55.1.44"},{"key":"b3-0250057","first-page":"4688","volume":"40","author":"Blackburn GR","year":"1980","journal-title":"Cancer Res"},{"key":"b4-0250057","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.971051196"},{"key":"b5-0250057","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/44.1.46"},{"key":"b6-0250057","doi-asserted-by":"publisher","DOI":"10.1089\/dna.1997.16.493"},{"key":"b7-0250057","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(87)90021-2"},{"key":"b8-0250057","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfh016"},{"key":"b9-0250057","first-page":"3847","volume":"63","author":"Gatenby RA","year":"2003","journal-title":"Cancer Res"},{"key":"b10-0250057","first-page":"242","volume":"29","author":"Gerbal-Chaloin S","year":"2001","journal-title":"Drug Metab Dispos"},{"key":"b11-0250057","first-page":"1","volume-title":"Handbook of carcinogenic potency and genotoxicity databases","author":"Gold LS","year":"1997"},{"key":"b12-0250057","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202000"},{"key":"b13-0250057","first-page":"609","volume-title":"Principles and methods of toxicology","author":"Guengerich FP","year":"1982"},{"key":"b14-0250057","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(81)77053-8"},{"key":"b15-0250057","doi-asserted-by":"publisher","DOI":"10.1023\/A:1026495911032"},{"key":"b16-0250057","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1110(94)90025-6"},{"key":"b17-0250057","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.10.5652"},{"key":"b18-0250057","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115672"},{"key":"b19-0250057","doi-asserted-by":"publisher","DOI":"10.1006\/abio.1994.1476"},{"key":"b20-0250057","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4274(99)00294-5"},{"key":"b21-0250057","doi-asserted-by":"publisher","DOI":"10.1172\/JCI3703"},{"key":"b22-0250057","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.19.3719"},{"key":"b23-0250057","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.10020"},{"key":"b24-0250057","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.13.10.6367"},{"key":"b25-0250057","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.9088207"},{"key":"b26-0250057","doi-asserted-by":"publisher","DOI":"10.1139\/o86-151"},{"key":"b27-0250057","first-page":"548","volume":"13","author":"Reinke LA","year":"1985","journal-title":"Drug Metab"},{"key":"b28-0250057","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1993.1121"},{"key":"b29-0250057","doi-asserted-by":"publisher","DOI":"10.1006\/rtph.2000.1427"},{"key":"b30-0250057","first-page":"486","volume":"38","author":"Srivastava G","year":"1990","journal-title":"Mol Pharmacol"},{"key":"b31-0250057","doi-asserted-by":"publisher","DOI":"10.3109\/00498258709044202"},{"key":"b32-0250057","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(01)01017-2"},{"key":"b33-0250057","first-page":"9","volume-title":"Health and disease","author":"Volanakis JE","year":"1998"},{"key":"b34-0250057","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/45.2.152"},{"key":"b35-0250057","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1827.2000.01132.x"},{"key":"b36-0250057","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.10.e48"},{"key":"b37-0250057","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1998.tb04307.x"}],"container-title":["International Journal of Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1080\/10915810500488429","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1080\/10915810500488429","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1080\/10915810500488429","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T10:22:18Z","timestamp":1777458138000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1080\/10915810500488429"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,1]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2006,1]]}},"alternative-id":["10.1080\/10915810500488429"],"URL":"https:\/\/doi.org\/10.1080\/10915810500488429","relation":{},"ISSN":["1091-5818","1092-874X"],"issn-type":[{"value":"1091-5818","type":"print"},{"value":"1092-874X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,1]]}}}