# HEPATIC OVAL CELLS IN CULTURE AND IN VIVO

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 1991 · $179,782

## Abstract

An improved intrahepatic biliary cell culture/in vivo transplantation
system has been established with an essentially pure population of
hyperplastic bile ductular epithelial cells isolated from cholestatic rat
liver at six or more weeks after bile duct ligation.  Based on an extended
characterization of this unique cell system, it is now apparent that it
possesses features which make it quite attractive for use in the analysis
of hyperplastic bile ductular epithelial cell function, growth control, and
carcinogenesis.  Moreover, this system has been developed to a point where
it now can be used to effectively investigate the relationship of the
hyperplastic bile ductular epithelial cells to proliferating "biliary oval
cells" that have been isolated and cultured from preneoplastic rat livers
during the early stages of hepatocarcinogenesis.  In this regard, this
continuation proposal focuses on achieving neoplastic transformation of
pure cultures of bile ductular epithelial cells from bile duct-ligated rats
(i.e., by in vitro treatments with the direct-acting carcinogen N-methyl-
N'-nitro-N-nitrosoquanidine or by transfection with the H-ras oncogene,
according to established procedure).  Particular attention will then be
paid to assessing the tumorigenicity of the biliary cell transformants
following inoculation of defined populations into the interscapular fat
pads or liver (via the portal vein) of syngeneic rats and/or nude mice.
Resulting tumors will be classified according to their type and level of
differentiation, as well as by their positive and negative expressions of
such phenotypic traits as cytokeratin 19, mucin production, alpha-
fetoprotein, hepatocyte antigen 368.7, gamma-glutamyl transpeptidase, and
glutathione S-transferase-P.  In addition, an effort will be made to
develop a novel multistage model of cholangiocarcinogenesis in rats, using
Furan as the initial carcinogenic stimulus.  A number of potential biliary
cell tumor promoters will then be evaluated for their ability to
specifically enhance the development of cholangiocellular carcinomas in
these animals.  It is anticipated that these studies will provide further
insight into the differentiation potential of the hyperplastic bile
ductular epithelial cell and its relationship to the "multipotential oval
cell", as well as lead to the development of valuable new models of in vivo
and in vitro cholangiocarcinogenesis.

## Key facts

- **NIH application ID:** 3178000
- **Project number:** 2R01CA039225-07
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **SAM.gov UEI:** MLQFL4JSSAA9
- **Principal Investigator:** ALPHONSE E SIRICA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $179,782
- **Award type:** 2
- **Project period:** 1984-07-01 → 1995-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178000

## Citation

> US National Institutes of Health, RePORTER application 3178000, HEPATIC OVAL CELLS IN CULTURE AND IN VIVO (2R01CA039225-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178000. Licensed CC0.

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