The relationship between HBV infection and the induction of hepatocellular carcinoma is currently enigmatic. We will explore several mechanisms that might account for association of HBV infection and liver tumor formation. We have observed instability in the genome of the host presenting with hepatocellular carcinoma and in chronic carriers of HBV. We therefore propose to explore the possibilities that HBV might integrate in specific areas of the host genome predisposed to instability that HBV might induce such genome destablization or that environmental factors or hereditary factors are at the root of the instability observed. Further, we propose to determine if genome instability is of predictive value in these tumors. We have established a panel of hepatocellular carcinoma-derived cell lines of hepatocyte morphology and function and plan to continue our analysis of their common chromosome aberrations. We propose to determine specific breakpoints common to these cell lines to identify specific areas of the genome which may contain genes responsible for the control of hepatocyte proliferation. By analysis of somatic cell hybrids, derived from fusion of human hepatocellular carcinoma-derived cell lines and stationary cultures of rat hepatocytes, and transfection of the stationary rat hepatocyte with cloned HBV and human hepatocellular carcinoma-derived DNA, we plan to distinguish between the direct oncogenic potenital of HBV and that of potentially activated human genes. Furthermore, identifiecation of a gene(s) of a gene product(s) that might effect such transformation is proposed.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA037225-08
Application #
3175030
Study Section
Virology Study Section (VR)
Project Start
1984-06-01
Project End
1993-03-31
Budget Start
1991-12-01
Budget End
1993-03-31
Support Year
8
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Wistar Institute
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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