| Treatment with 2-AAF blocks the small hepatocyte-like progenitor cell response in retrorsine-exposed rats. | |
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MedLine Citation:
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PMID: 17434228 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND/AIMS: Liver regeneration after partial hepatectomy (PH) in retrorsine-exposed rats is accomplished through proliferation and differentiation of small hepatocyte-like progenitor cells (SHPCs). The cells of origin of SHPCs are not known. We investigated the possibility that SHPCs are directly derived from oval cells, a known liver progenitor cell, by combining the retrorsine/PH (RP) model with 2-acetamidofluorene (2-AAF), an anti-mitotic agent that elicits an oval cell reaction in response to liver deficit. METHODS: Male Fischer 344 rats were treated with retrorsine (30 mg/kg ip) at 6 and 8 weeks of age, with PH 5 weeks after the final treatment. Seven days prior to PH, a 21-day 2-AAF (50mg) time-release pellet was inserted subcutaneously. Livers were harvested at 3, 7, 10, 14, and 21-days post-PH. RESULTS: Liver sections from animals treated with 2-AAF/retrorsine/PH (2-AAF/RP) contain significant numbers of proliferating oval cells, but no SHPCs at 7-days post-PH, while RP animals exhibit significant numbers of SHPCs and minimal oval cell reaction. Between 10 and 14-days post-PH, new hepatocyte clusters appear in 2-AAF/RP treated rats. Labeling of proliferating oval cells with BrdU at 6-days post-PH demonstrated that these new hepatocytes represent the progeny of differentiating oval cells. CONCLUSIONS: The observed differences in progenitor cell responses between 2-AAF/RP and RP animals strongly suggest that SHPCs are not the progeny of oval cell precursors, but represent an independent liver progenitor cell population. |
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Authors:
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D Hunter Best; William B Coleman |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2007-03-08 |
Journal Detail:
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Title: Journal of hepatology Volume: 46 ISSN: 0168-8278 ISO Abbreviation: J. Hepatol. Publication Date: 2007 Jun |
Date Detail:
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Created Date: 2007-05-07 Completed Date: 2007-08-15 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 8503886 Medline TA: J Hepatol Country: England |
Other Details:
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Languages: eng Pagination: 1055-63 Citation Subset: IM |
Affiliation:
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Department of Pathology and Laboratory Medicine, Curriculum in Toxicology, UNC Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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2-Acetylaminofluorene* Animals Antimitotic Agents / pharmacology Antineoplastic Agents, Phytogenic / pharmacology* Carcinogens* Cell Proliferation Hepatocytes / drug effects* Liver / pathology Liver Regeneration Male Pyrrolizidine Alkaloids / pharmacology Rats Rats, Inbred F344 Regeneration / drug effects Stem Cells / drug effects*, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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CA 78343/CA/NCI NIH HHS; R01 CA078434-10/CA/NCI NIH HHS; T32 ES 07017/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antimitotic Agents; 0/Antineoplastic Agents, Phytogenic; 0/Carcinogens; 0/Pyrrolizidine Alkaloids; 480-54-6/retrorsine; 53-96-3/2-Acetylaminofluorene |
| Comments/Corrections | |
Comment In:
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J Hepatol. 2008 Feb;48(2):368-9
[PMID:
18093688
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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