The fumonisin B₁-fed rat as a model for liver injury, oval ('progenitor') cell proliferation, and carcinogenesis

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dc.contributor.advisorHall, Paulineen_ZA
dc.contributor.advisorShephard, Eniden_ZA
dc.contributor.advisorCruse, Peteren_ZA
dc.contributor.authorLemmer, Eric Richarden_ZA
dc.date.accessioned2015-09-25T07:06:29Z
dc.date.available2015-09-25T07:06:29Z
dc.date.issued1999en_ZA
dc.descriptionBibliography: leaves 142-170.en_ZA
dc.description.abstractFumonisin B₁ (FB₁‚ ) is a carcinogenic mycotoxin produced by the fimgus Fusarium moniliforme in maize, and is hepatotoxic and hepatocarcinogenic in rats. The goal of this dissertation was to characterise the FB₁-fed rat as a model for liver injury and carcinogenesis, and to examine the role of oval ('progenitor') cells during these processes. Male Fischer 344 rats were fed FB₁ 250 mg/kg diet for five weeks, and this basic feeding regimen was modified in individual experiments. Short-term feeding of FB₁ caused a severe 'toxic' hepatitis, apoptosis and regeneration of hepatocytes, fibrosis, proliferation of OV-6 positive oval cells, and formation of GST pi positive hepatic foci and nodules. Oval cells were noted inside some of the hepatic nodules. There were marked increases in the expression of mRNA transcripts for mature TGF-β1 and c-myc in livers of FB₁-fed animals. The overexpression of TGF-β1 by hepatocytes may be responsible for the prominent apoptosis and fibrosis seen with liver injury due to FB₁. Increased expression of c-myc and TGF-β1 may cooperate during FB₁-induced promotion of liver tumours, possibly by providing an environment that selects for the growth of TGFβ1-resistant transformed liver cells. In rats given FB₁ in the presence of dietary iron overload, FB₁ augmented iron-induced lipid peroxidation in the liver. However, dietary iron loading appeared to protect against the cancer-promoting properties of FB₁, possibly due to a stimulatory effect on hepatocyte regeneration. Long-term feeding of FB₁ caused fibrosis and regenerative nodules, dysplastic hepatic nodules, cholangiofibrotic lesions, intraductal cholangiocarcinomas, and a hepatocellular carcinoma. 2-Acetylaminofluorene enhanced the effects of FB₁ in the liver, presumably by blocking hepatocyte regeneration in response to FB₁ toxicity. Proliferating oval cells were found inside/adjacent to GST pi positive lesions, dysplastic nodules, and cholangiofibrotic lesions, suggesting that oval cells may be involved in FBI-induced hepato- and cholangiocarcinogenesis in the liver. Furthermore, the OV-6 antigen was expressed by proliferating oval cells and bile ductules, hepatic nodules, cholangiofibrotic lesions, and cystic lesions, indicating that all of these cells may have a common ('stem') cell of origin. In conclusion, the FB₁-fed rat is a promising model for the study of liver injury, oval ('progenitor') cell proliferation, and carcinogenesis.en_ZA
dc.identifier.apacitationLemmer, E. R. (1999). <i>The fumonisin B₁-fed rat as a model for liver injury, oval ('progenitor') cell proliferation, and carcinogenesis</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,UCT/MRC Liver Research Centre. Retrieved from http://hdl.handle.net/11427/14071en_ZA
dc.identifier.chicagocitationLemmer, Eric Richard. <i>"The fumonisin B₁-fed rat as a model for liver injury, oval ('progenitor') cell proliferation, and carcinogenesis."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,UCT/MRC Liver Research Centre, 1999. http://hdl.handle.net/11427/14071en_ZA
dc.identifier.citationLemmer, E. 1999. The fumonisin B₁-fed rat as a model for liver injury, oval ('progenitor') cell proliferation, and carcinogenesis. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Lemmer, Eric Richard AB - Fumonisin B₁ (FB₁‚ ) is a carcinogenic mycotoxin produced by the fimgus Fusarium moniliforme in maize, and is hepatotoxic and hepatocarcinogenic in rats. The goal of this dissertation was to characterise the FB₁-fed rat as a model for liver injury and carcinogenesis, and to examine the role of oval ('progenitor') cells during these processes. Male Fischer 344 rats were fed FB₁ 250 mg/kg diet for five weeks, and this basic feeding regimen was modified in individual experiments. Short-term feeding of FB₁ caused a severe 'toxic' hepatitis, apoptosis and regeneration of hepatocytes, fibrosis, proliferation of OV-6 positive oval cells, and formation of GST pi positive hepatic foci and nodules. Oval cells were noted inside some of the hepatic nodules. There were marked increases in the expression of mRNA transcripts for mature TGF-β1 and c-myc in livers of FB₁-fed animals. The overexpression of TGF-β1 by hepatocytes may be responsible for the prominent apoptosis and fibrosis seen with liver injury due to FB₁. Increased expression of c-myc and TGF-β1 may cooperate during FB₁-induced promotion of liver tumours, possibly by providing an environment that selects for the growth of TGFβ1-resistant transformed liver cells. In rats given FB₁ in the presence of dietary iron overload, FB₁ augmented iron-induced lipid peroxidation in the liver. However, dietary iron loading appeared to protect against the cancer-promoting properties of FB₁, possibly due to a stimulatory effect on hepatocyte regeneration. Long-term feeding of FB₁ caused fibrosis and regenerative nodules, dysplastic hepatic nodules, cholangiofibrotic lesions, intraductal cholangiocarcinomas, and a hepatocellular carcinoma. 2-Acetylaminofluorene enhanced the effects of FB₁ in the liver, presumably by blocking hepatocyte regeneration in response to FB₁ toxicity. Proliferating oval cells were found inside/adjacent to GST pi positive lesions, dysplastic nodules, and cholangiofibrotic lesions, suggesting that oval cells may be involved in FBI-induced hepato- and cholangiocarcinogenesis in the liver. Furthermore, the OV-6 antigen was expressed by proliferating oval cells and bile ductules, hepatic nodules, cholangiofibrotic lesions, and cystic lesions, indicating that all of these cells may have a common ('stem') cell of origin. In conclusion, the FB₁-fed rat is a promising model for the study of liver injury, oval ('progenitor') cell proliferation, and carcinogenesis. DA - 1999 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 1999 T1 - The fumonisin B₁-fed rat as a model for liver injury, oval ('progenitor') cell proliferation, and carcinogenesis TI - The fumonisin B₁-fed rat as a model for liver injury, oval ('progenitor') cell proliferation, and carcinogenesis UR - http://hdl.handle.net/11427/14071 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/14071
dc.identifier.vancouvercitationLemmer ER. The fumonisin B₁-fed rat as a model for liver injury, oval ('progenitor') cell proliferation, and carcinogenesis. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,UCT/MRC Liver Research Centre, 1999 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/14071en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentUCT/MRC Liver Research Centreen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherLiver Researchen_ZA
dc.titleThe fumonisin B₁-fed rat as a model for liver injury, oval ('progenitor') cell proliferation, and carcinogenesisen_ZA
dc.typeDoctoral Thesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnamePhDen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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