Full Text Available
Note: Clicking the button above will open the full text document at the original institutional repository in a new window.
The fumonisin B₁-fed rat as a model for liver injury, oval ('progenitor') cell proliferation, and carcinogenesis
Bibliography: leaves 142-170.
Saved in:
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Language: | English |
| Published: |
UCT/MRC Liver Research Centre
2015
|
| Subjects: | |
| Tags: |
No Tags, Be the first to tag this record!
|
| _version_ | 1867613253732925440 |
|---|---|
| access_status_str | Open Access |
| author | Lemmer, Eric Richard |
| author2 | Hall, Pauline |
| author_browse | Hall, Pauline Lemmer, Eric Richard |
| author_facet | Hall, Pauline Lemmer, Eric Richard |
| author_sort | Lemmer, Eric Richard |
| collection | Thesis |
| description | Bibliography: leaves 142-170. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/14071 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:33:12.104Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2015 |
| publishDateRange | 2015 |
| publishDateSort | 2015 |
| publisher | UCT/MRC Liver Research Centre |
| publisherStr | UCT/MRC Liver Research Centre |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/14071 The fumonisin B₁-fed rat as a model for liver injury, oval ('progenitor') cell proliferation, and carcinogenesis Lemmer, Eric Richard Hall, Pauline Shephard, Enid Cruse, Peter Liver Research Bibliography: leaves 142-170. 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. 2015-09-25T07:06:29Z 2015-09-25T07:06:29Z 1999 Doctoral Thesis Doctoral PhD http://hdl.handle.net/11427/14071 eng application/pdf UCT/MRC Liver Research Centre Faculty of Health Sciences University of Cape Town |
| spellingShingle | Liver Research Lemmer, Eric Richard The fumonisin B₁-fed rat as a model for liver injury, oval ('progenitor') cell proliferation, and carcinogenesis |
| thesis_degree_str | Doctoral |
| title | The fumonisin B₁-fed rat as a model for liver injury, oval ('progenitor') cell proliferation, and carcinogenesis |
| title_full | The fumonisin B₁-fed rat as a model for liver injury, oval ('progenitor') cell proliferation, and carcinogenesis |
| title_fullStr | The fumonisin B₁-fed rat as a model for liver injury, oval ('progenitor') cell proliferation, and carcinogenesis |
| title_full_unstemmed | The fumonisin B₁-fed rat as a model for liver injury, oval ('progenitor') cell proliferation, and carcinogenesis |
| title_short | The fumonisin B₁-fed rat as a model for liver injury, oval ('progenitor') cell proliferation, and carcinogenesis |
| title_sort | fumonisin b₁ fed rat as a model for liver injury oval progenitor cell proliferation and carcinogenesis |
| topic | Liver Research |
| url | http://hdl.handle.net/11427/14071 |
| work_keys_str_mv | AT lemmerericrichard thefumonisinb1fedratasamodelforliverinjuryovalprogenitorcellproliferationandcarcinogenesis AT lemmerericrichard fumonisinb1fedratasamodelforliverinjuryovalprogenitorcellproliferationandcarcinogenesis |