# ALLOANTIGENS AS PROBES FOR HEPATOCARCINOGENESIS

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 1987 · $111,029

## Abstract

Chemically induced hepatocarcinogenesis in rats will be studied
from the standpoint of the RT1 major histocompatibility complex
Class I alloantigens expressed on the surface of liver cells.  The
working hypothesis is that during carcinogen-induced evolution of
certain normal liver cells into carcinomas, detectable changes in
RT1 Class I alloantigens on premalignant liver cells occur,
indicative of functional alterations in cellular growth control
mechanisms in these carcinoma precursor cell subpopulations.

The genotypic mosaic liver model of hepatocarcinogenesis will be
used to generate donor origin premalignant liver lesions in hybrid
host rat livers.  Donor origin lesions identified in histologic
sections by indirect immunofluorescence using rat strain-specific
alloantisera will be histochemically characterized, then puch-
dissected for analysis in situ of alloantigen expression by the
lesion cells.  The punch-dissected lesion tissue microsamples will
be detergent-extracted, and the cell proteins radioiodinated,
immunoprecipitated, and analyzed by 2-D IEF/SDS-PAGE.
Altered alloantigen expression will be scored from gel
autoradiograms as a potentially new marker of authentic
carcinoma precursor cells.

Donor origin premalignant liver cells will be purified from cell
suspensions prepared using strain-specific alloantisera for
complement mediated cytolysis.  The purified cells will be placed
in short-term (less than 24hr) culture for radiolabeling
alloantigens using 35S-methionine.  Altered alloantigen expression
by these cells will be compared with in situ expression, and may
represent a new marker for premalignant liver cells in culture.

Finally, the genotypic mosaic model will be used to trace the fate
of subpopulations of donor liver cells in host rat livers.  Donor
liver cells will be reacted prior to transplantation with a panel of
monoclonal antibodies (mAb) specific for epitopes of premalignant
and malignant liver cells.  Donor liver cells "targeted" by reaction
with particular mAb will be selectively removed or killed.
Immunohistochemical characterization of the development of
donor origin lesions over a 17-month period will identify lesions
arising from non-targeted donor liver cells.  These transplantation
experiments are expected to identify precursor cells of
phenotypically distinct donor origin liver lesions, inlcuding
hepatocellular carcinomas.  The ultimate goal of these studies is
to identify, as early as possible, the authentic cellular precursors
of hepatocellular carcinomas.  The elimination of these
premalignant cells could eventually serve as a novel preventive
therapy for primary human liver cancer.

## Key facts

- **NIH application ID:** 3174882
- **Project number:** 2R01CA037150-04A1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **SAM.gov UEI:** ZUFBNVZ587D4
- **Principal Investigator:** JOHN M HUNT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $111,029
- **Award type:** 2
- **Project period:** 1984-03-01 → 1990-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174882

## Citation

> US National Institutes of Health, RePORTER application 3174882, ALLOANTIGENS AS PROBES FOR HEPATOCARCINOGENESIS (2R01CA037150-04A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174882. Licensed CC0.

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