Document Detail

Treatment with 2-AAF blocks the small hepatocyte-like progenitor cell response in retrorsine-exposed rats.
MedLine Citation:
PMID:  17434228     Owner:  NLM     Status:  MEDLINE    
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.
D Hunter Best; William B Coleman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-03-08
Journal Detail:
Title:  Journal of hepatology     Volume:  46     ISSN:  0168-8278     ISO Abbreviation:  J. Hepatol.     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-05-07     Completed Date:  2007-08-15     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1055-63     Citation Subset:  IM    
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.
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MeSH Terms
Antimitotic Agents / pharmacology
Antineoplastic Agents, Phytogenic / pharmacology*
Cell Proliferation
Hepatocytes / drug effects*
Liver / pathology
Liver Regeneration
Pyrrolizidine Alkaloids / pharmacology
Rats, Inbred F344
Regeneration / drug effects
Stem Cells / drug effects*,  metabolism
Grant Support
CA 78343/CA/NCI NIH HHS; R01 CA078434-10/CA/NCI NIH HHS; T32 ES 07017/ES/NIEHS NIH HHS
Reg. No./Substance:
0/Antimitotic Agents; 0/Antineoplastic Agents, Phytogenic; 0/Carcinogens; 0/Pyrrolizidine Alkaloids; 480-54-6/retrorsine; 53-96-3/2-Acetylaminofluorene
Comment In:
J Hepatol. 2008 Feb;48(2):368-9   [PMID:  18093688 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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