# WHV AND HBV ASSOCIATED HEPATOCELLULAR CARCINOMA

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 1989 · $296,720

## Abstract

The overall emphasis will be to investigate the role of HBV and WHV in
hepatic oncogenesis.  The significance and specificity of chromosome
aberrations and Insulin-like growth factor II activation associated with
HCC in hepadna virus carriers will be investigated.  Cell culture assays
and "in vivo" hepatocarcinogenesis studies in woodchucks will test
mechanisms of HBV and WHV induced carcinogenesis.  Specific studies to be
conducted include:

1. Analysis of loss or amplification of alleles from specific chromosomes
in primary human HCC.  In this study we will determine (a) the extent and
frequency of deletions in chromosome llp in HCCs using the loss of
restriction fragment length polymorphisms (RFLPs) as an assay for loss of
alleles, (b) the frequency of loss or amplification of alleles in
chromosomes other than 11 and (c) the copy number, hemizygous, homozygous
(reduplicated) or amplified, of the polymorphic alleles remaining after
loss of their homologue and the relationship (if any) of HBV integration to
loss of alleles on chromosomes containing these integrations.

2. Determine the frequency, specificity and mechanisms of transcriptional
activation of IGF-II in primary woodchuck HCCs.  The abundance and sizes
aof IGFD-II RNAs intissues at stages of hepatic oncogenesis, inwoodchucks
will be studied along with the specificity of IGF-II activation, and the
mechanism of IGF-II transcription by sequencing cDNA clones of IGF-II mRNAs
from woodchuck HCCs.

3. Analyze the activity of integrated HBV and WHY DNA using biological
assays for tumorigenesis and transcription.  Cell lines contain HBV and WHV
constructs will be used to address the following questions (a) can HBV and
WHV function in a "Hit and Run" tumorigenesis mechanism and do they affect
the mutation rate of cellular genes and (b) how do HBV integrations
containing enhancer elements affect transcription of cellular genes
flanking HBV.

4. Experimental manipulation of HCC in woodchucks and isolation of
woodchuck hepatocyte cell lines.  Partial hepatectomy and CC14 and
phenobarbitol treatments will be used to manipulate HCC in woodchucks.
Preneoplastic nodules and HCCs will be analyzed for WHV integration and
IGF-II activation to study events proceeding HCC.  Woodchuck hepatocyte
cell cultures will be initiated using newly developed methods of Kitagawa
to study WHV replication and progression to HCC.

## Key facts

- **NIH application ID:** 3175040
- **Project number:** 5R01CA037232-06
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Charles E. Rogler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $296,720
- **Award type:** 5
- **Project period:** 1984-04-01 → 1992-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175040

## Citation

> US National Institutes of Health, RePORTER application 3175040, WHV AND HBV ASSOCIATED HEPATOCELLULAR CARCINOMA (5R01CA037232-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3175040. Licensed CC0.

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