Neoplastic and Nonneoplastic Liver Lesions Induced by Dimethylnitrosamine in Japanese Medaka Fish
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 cirr...
Gespeichert in:
Veröffentlicht in: | Veterinary pathology 2012-03, Vol.49 (2), p.372-385 |
---|---|
Hauptverfasser: | , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 385 |
---|---|
container_issue | 2 |
container_start_page | 372 |
container_title | Veterinary pathology |
container_volume | 49 |
creator | Hobbie, K. R. DeAngelo, A. B. George, M. H. Law, J. M. |
description | 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® 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-β pathway and its corresponding role in DMN-induced hepatic neoplasia. Similar to mammals, hepatocellular necrosis, regeneration, and dysplasia; hepatic stellate cell and “spindle cell” proliferation; hepatocellular and biliary carcinomas; and TGF-β1 expression by dysplastic hepatocytes all occurred in DMN-exposed medaka. Positive TGF-β1 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. |
doi_str_mv | 10.1177/0300985811409443 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1712768163</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1177_0300985811409443</sage_id><sourcerecordid>1712768163</sourcerecordid><originalsourceid>FETCH-LOGICAL-c477t-eeb5cfa2f16aa3c97712f8729074cb7febc7075c0e8c3854880e6670ab6379e23</originalsourceid><addsrcrecordid>eNp1kDFPwzAQhS0EoqWwMyGPLAHbcXLOiAqFolIWmCPHuVCXxAlxgtR_T6oWkJCYTrr3vae7R8g5Z1ecA1yzkLFERYpzyRIpwwMy5pGUgRAcDsl4KwdbfUROvF8zJkSi4JiMBlnIBOIx0Uusm1L7zhqqXU6XtXO_m4X9xJYu0NvaeTp3eW8wp9mG3toKu9WmdLZra68r65BaRx91ox16pE-Y63dNZ9avTslRoUuPZ_s5Ia-zu5fpQ7B4vp9PbxaBkQBdgJhFptCi4LHWoUkAuCgUiISBNBkUmBlgEBmGyoQqkkoxjGNgOotDSFCEE3K5y23a-qNH36WV9QbLcrio7n3Kh0CIFY_DAWU71AzH-xaLtGltpdtNylm6LTb9W-xgudin91mF-Y_hu8kBCHaA12-Yruu-dcO3_wd-ASO4gFU</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1712768163</pqid></control><display><type>article</type><title>Neoplastic and Nonneoplastic Liver Lesions Induced by Dimethylnitrosamine in Japanese Medaka Fish</title><source>Access via SAGE</source><source>MEDLINE</source><creator>Hobbie, K. R. ; DeAngelo, A. B. ; George, M. H. ; Law, J. M.</creator><creatorcontrib>Hobbie, K. R. ; DeAngelo, A. B. ; George, M. H. ; Law, J. M.</creatorcontrib><description>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® 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-β pathway and its corresponding role in DMN-induced hepatic neoplasia. Similar to mammals, hepatocellular necrosis, regeneration, and dysplasia; hepatic stellate cell and “spindle cell” proliferation; hepatocellular and biliary carcinomas; and TGF-β1 expression by dysplastic hepatocytes all occurred in DMN-exposed medaka. Positive TGF-β1 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.</description><identifier>ISSN: 0300-9858</identifier><identifier>EISSN: 1544-2217</identifier><identifier>DOI: 10.1177/0300985811409443</identifier><identifier>PMID: 21724976</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>Animals ; Animals, Genetically Modified ; Biliary Tract Neoplasms - chemically induced ; Biliary Tract Neoplasms - pathology ; Biliary Tract Neoplasms - veterinary ; Biomarkers - metabolism ; Carcinogenicity Tests ; Carcinogens - toxicity ; Carcinoma, Hepatocellular - chemically induced ; Carcinoma, Hepatocellular - pathology ; Carcinoma, Hepatocellular - veterinary ; Cell Proliferation - drug effects ; Chemical and Drug Induced Liver Injury - pathology ; Chemical and Drug Induced Liver Injury - veterinary ; Dimethylnitrosamine - toxicity ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Female ; Fish Diseases - chemically induced ; Fish Diseases - pathology ; Liver - drug effects ; Liver Neoplasms - chemically induced ; Liver Neoplasms - pathology ; Liver Neoplasms - veterinary ; Male ; Mutagenicity Tests ; Oryzias ; Oryzias latipes ; Rats ; Signal Transduction ; Species Specificity ; Transforming Growth Factor beta - metabolism</subject><ispartof>Veterinary pathology, 2012-03, Vol.49 (2), p.372-385</ispartof><rights>American College of Veterinary Pathologists 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c477t-eeb5cfa2f16aa3c97712f8729074cb7febc7075c0e8c3854880e6670ab6379e23</citedby><cites>FETCH-LOGICAL-c477t-eeb5cfa2f16aa3c97712f8729074cb7febc7075c0e8c3854880e6670ab6379e23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/0300985811409443$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/0300985811409443$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,780,784,21819,27924,27925,43621,43622</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21724976$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hobbie, K. R.</creatorcontrib><creatorcontrib>DeAngelo, A. B.</creatorcontrib><creatorcontrib>George, M. H.</creatorcontrib><creatorcontrib>Law, J. M.</creatorcontrib><title>Neoplastic and Nonneoplastic Liver Lesions Induced by Dimethylnitrosamine in Japanese Medaka Fish</title><title>Veterinary pathology</title><addtitle>Vet Pathol</addtitle><description>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® 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-β pathway and its corresponding role in DMN-induced hepatic neoplasia. Similar to mammals, hepatocellular necrosis, regeneration, and dysplasia; hepatic stellate cell and “spindle cell” proliferation; hepatocellular and biliary carcinomas; and TGF-β1 expression by dysplastic hepatocytes all occurred in DMN-exposed medaka. Positive TGF-β1 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.</description><subject>Animals</subject><subject>Animals, Genetically Modified</subject><subject>Biliary Tract Neoplasms - chemically induced</subject><subject>Biliary Tract Neoplasms - pathology</subject><subject>Biliary Tract Neoplasms - veterinary</subject><subject>Biomarkers - metabolism</subject><subject>Carcinogenicity Tests</subject><subject>Carcinogens - toxicity</subject><subject>Carcinoma, Hepatocellular - chemically induced</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Carcinoma, Hepatocellular - veterinary</subject><subject>Cell Proliferation - drug effects</subject><subject>Chemical and Drug Induced Liver Injury - pathology</subject><subject>Chemical and Drug Induced Liver Injury - veterinary</subject><subject>Dimethylnitrosamine - toxicity</subject><subject>Disease Models, Animal</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Fish Diseases - chemically induced</subject><subject>Fish Diseases - pathology</subject><subject>Liver - drug effects</subject><subject>Liver Neoplasms - chemically induced</subject><subject>Liver Neoplasms - pathology</subject><subject>Liver Neoplasms - veterinary</subject><subject>Male</subject><subject>Mutagenicity Tests</subject><subject>Oryzias</subject><subject>Oryzias latipes</subject><subject>Rats</subject><subject>Signal Transduction</subject><subject>Species Specificity</subject><subject>Transforming Growth Factor beta - metabolism</subject><issn>0300-9858</issn><issn>1544-2217</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kDFPwzAQhS0EoqWwMyGPLAHbcXLOiAqFolIWmCPHuVCXxAlxgtR_T6oWkJCYTrr3vae7R8g5Z1ecA1yzkLFERYpzyRIpwwMy5pGUgRAcDsl4KwdbfUROvF8zJkSi4JiMBlnIBOIx0Uusm1L7zhqqXU6XtXO_m4X9xJYu0NvaeTp3eW8wp9mG3toKu9WmdLZra68r65BaRx91ox16pE-Y63dNZ9avTslRoUuPZ_s5Ia-zu5fpQ7B4vp9PbxaBkQBdgJhFptCi4LHWoUkAuCgUiISBNBkUmBlgEBmGyoQqkkoxjGNgOotDSFCEE3K5y23a-qNH36WV9QbLcrio7n3Kh0CIFY_DAWU71AzH-xaLtGltpdtNylm6LTb9W-xgudin91mF-Y_hu8kBCHaA12-Yruu-dcO3_wd-ASO4gFU</recordid><startdate>20120301</startdate><enddate>20120301</enddate><creator>Hobbie, K. R.</creator><creator>DeAngelo, A. B.</creator><creator>George, M. H.</creator><creator>Law, J. M.</creator><general>SAGE Publications</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>F1W</scope><scope>H95</scope><scope>L.G</scope></search><sort><creationdate>20120301</creationdate><title>Neoplastic and Nonneoplastic Liver Lesions Induced by Dimethylnitrosamine in Japanese Medaka Fish</title><author>Hobbie, K. R. ; DeAngelo, A. B. ; George, M. H. ; Law, J. M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c477t-eeb5cfa2f16aa3c97712f8729074cb7febc7075c0e8c3854880e6670ab6379e23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Animals, Genetically Modified</topic><topic>Biliary Tract Neoplasms - chemically induced</topic><topic>Biliary Tract Neoplasms - pathology</topic><topic>Biliary Tract Neoplasms - veterinary</topic><topic>Biomarkers - metabolism</topic><topic>Carcinogenicity Tests</topic><topic>Carcinogens - toxicity</topic><topic>Carcinoma, Hepatocellular - chemically induced</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Carcinoma, Hepatocellular - veterinary</topic><topic>Cell Proliferation - drug effects</topic><topic>Chemical and Drug Induced Liver Injury - pathology</topic><topic>Chemical and Drug Induced Liver Injury - veterinary</topic><topic>Dimethylnitrosamine - toxicity</topic><topic>Disease Models, Animal</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Fish Diseases - chemically induced</topic><topic>Fish Diseases - pathology</topic><topic>Liver - drug effects</topic><topic>Liver Neoplasms - chemically induced</topic><topic>Liver Neoplasms - pathology</topic><topic>Liver Neoplasms - veterinary</topic><topic>Male</topic><topic>Mutagenicity Tests</topic><topic>Oryzias</topic><topic>Oryzias latipes</topic><topic>Rats</topic><topic>Signal Transduction</topic><topic>Species Specificity</topic><topic>Transforming Growth Factor beta - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hobbie, K. R.</creatorcontrib><creatorcontrib>DeAngelo, A. B.</creatorcontrib><creatorcontrib>George, M. H.</creatorcontrib><creatorcontrib>Law, J. M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><jtitle>Veterinary pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hobbie, K. R.</au><au>DeAngelo, A. B.</au><au>George, M. H.</au><au>Law, J. M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neoplastic and Nonneoplastic Liver Lesions Induced by Dimethylnitrosamine in Japanese Medaka Fish</atitle><jtitle>Veterinary pathology</jtitle><addtitle>Vet Pathol</addtitle><date>2012-03-01</date><risdate>2012</risdate><volume>49</volume><issue>2</issue><spage>372</spage><epage>385</epage><pages>372-385</pages><issn>0300-9858</issn><eissn>1544-2217</eissn><abstract>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® 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-β pathway and its corresponding role in DMN-induced hepatic neoplasia. Similar to mammals, hepatocellular necrosis, regeneration, and dysplasia; hepatic stellate cell and “spindle cell” proliferation; hepatocellular and biliary carcinomas; and TGF-β1 expression by dysplastic hepatocytes all occurred in DMN-exposed medaka. Positive TGF-β1 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.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>21724976</pmid><doi>10.1177/0300985811409443</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0300-9858 |
ispartof | Veterinary pathology, 2012-03, Vol.49 (2), p.372-385 |
issn | 0300-9858 1544-2217 |
language | eng |
recordid | cdi_proquest_miscellaneous_1712768163 |
source | Access via SAGE; MEDLINE |
subjects | Animals Animals, Genetically Modified Biliary Tract Neoplasms - chemically induced Biliary Tract Neoplasms - pathology Biliary Tract Neoplasms - veterinary Biomarkers - metabolism Carcinogenicity Tests Carcinogens - toxicity Carcinoma, Hepatocellular - chemically induced Carcinoma, Hepatocellular - pathology Carcinoma, Hepatocellular - veterinary Cell Proliferation - drug effects Chemical and Drug Induced Liver Injury - pathology Chemical and Drug Induced Liver Injury - veterinary Dimethylnitrosamine - toxicity Disease Models, Animal Dose-Response Relationship, Drug Female Fish Diseases - chemically induced Fish Diseases - pathology Liver - drug effects Liver Neoplasms - chemically induced Liver Neoplasms - pathology Liver Neoplasms - veterinary Male Mutagenicity Tests Oryzias Oryzias latipes Rats Signal Transduction Species Specificity Transforming Growth Factor beta - metabolism |
title | Neoplastic and Nonneoplastic Liver Lesions Induced by Dimethylnitrosamine in Japanese Medaka Fish |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T10%3A18%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Neoplastic%20and%20Nonneoplastic%20Liver%20Lesions%20Induced%20by%20Dimethylnitrosamine%20in%20Japanese%20Medaka%20Fish&rft.jtitle=Veterinary%20pathology&rft.au=Hobbie,%20K.%20R.&rft.date=2012-03-01&rft.volume=49&rft.issue=2&rft.spage=372&rft.epage=385&rft.pages=372-385&rft.issn=0300-9858&rft.eissn=1544-2217&rft_id=info:doi/10.1177/0300985811409443&rft_dat=%3Cproquest_cross%3E1712768163%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1712768163&rft_id=info:pmid/21724976&rft_sage_id=10.1177_0300985811409443&rfr_iscdi=true |