{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T07:12:21Z","timestamp":1791097941829,"version":"4.1.0"},"reference-count":46,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2011,7,1]],"date-time":"2011-07-01T00:00:00Z","timestamp":1309478400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Vet Pathol"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:p>\n                    Small fish models have been used for decades in carcinogenicity testing. Demonstration of common morphological changes associated with specific mechanisms is a clear avenue by which data can be compared across divergent phyletic levels. Dimethylnitrosamine, used in rats to model human alcoholic cirrhosis and hepatic neoplasia, is also a potent hepatotoxin and carcinogen in fish. We recently reported some striking differences in the mutagenicity of DMN in lambda cII transgenic medaka fish vs. Big Blue\n                    <jats:sup>\u00ae<\/jats:sup>\n                    rats, but the pre-neoplastic and neoplastic commonalities between the two models are largely unknown. Here, we focus on these commonalities, with special emphasis on the TGF-\n                    <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                    pathway and its corresponding role in DMN-induced hepatic neoplasia. Similar to mammals, hepatocellular necrosis, regeneration, and dysplasia; hepatic stellate cell and \u201cspindle cell\u201d proliferation; hepatocellular and biliary carcinomas; and TGF-\u03b21 expression by dysplastic hepatocytes all occurred in DMN-exposed medaka. Positive TGF-\n                    <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                    1 staining increased with increasing DMN exposure in bile preductular epithelial cells, intermediate cells, immature hepatocytes and fewer mature hepatocytes. Muscle specific actin identified hepatic stellate cells in DMN-exposed fish. Additional mechanistic comparisons between animal models at different phyletic levels will continue to facilitate the interspecies extrapolations that are so critical to toxicological risk assessments.\n                  <\/jats:p>","DOI":"10.1177\/0300985811409443","type":"journal-article","created":{"date-parts":[[2011,7,4]],"date-time":"2011-07-04T07:10:56Z","timestamp":1309763456000},"page":"372-385","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":17,"title":["Neoplastic and Nonneoplastic Liver Lesions Induced by Dimethylnitrosamine in Japanese Medaka Fish"],"prefix":"10.1177","volume":"49","author":[{"given":"K. R.","family":"Hobbie","sequence":"first","affiliation":[{"name":"Integrated Laboratory Systems, Research Triangle Park, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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M.","family":"Law","sequence":"additional","affiliation":[{"name":"Department of Population Health and Pathobiology and Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, North Carolina State University, Raleigh, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2011,7]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.96104s15"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.28457"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1177\/019262339702500210"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/16.5.1059"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1746.2003.03162.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.20750"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706172"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(00)00056-1"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.02.047"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0959-9673.2004.00377.x"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.4.2247"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2006.07.002"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(03)00253-X"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/60.5.1127"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/ar.20524"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1006\/fsim.1999.0230"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1177\/002215540205001105"},{"issue":"1","key":"e_1_3_3_19_2","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1080\/01926230309771","article-title":"Use of the Japanese medaka (Oryzias latipes) and Guppy (Poecilia reticulata) in carcinogenesis testing under National Toxicology Program protocols","volume":"31","author":"Hawkins WE","year":"2003","unstructured":"Hawkins WE, Walker WW, Fournie JW, Manning CS, Krol RM. 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