Expression of p53 gene in hepatocellular carcinomas induced by aflatoxin B1 with or without human hepatitis B virus in tree shrews

ABSTRACT

Using tree shrew as an animal model, our previous studies have demonstrated synergistic effects of aflatoxin B-1 (AFB(1)) and human hepatitis B virus (HHBV) in the induction of hepatocellular carcinoma (HCC). In the present study, we have examined expression of p53 gene in HCCs induced by AFB(1) with or without HHBV infection in tree shrews. Avidin-biotin-peroxidase complex immunohistochemical method with human p53-CM1 polyclonal antibody has been used to detect p53 expression in serial sections of paraffin-embedded liver and HCC tissues. Five out of 9 animals with HCCs (55.6%) induced by AFB(1) with HHBV infection and 2/3 animals with HCCs (66.7%) induced by AFB(1) alone expressed the p53 protein. Out of 18 HCCs examined, expression of p53 protein was observed in 9/10 moderately and poorly differentiated HCCs (0/8). None of the well differentiated HCCs (0/8) expressed p53 (0%). Similarly, no p53 expression was observed in either non-tumorous or hyperplastic liver tissues or nodules. These results suggest that p53 expression associated with p53 mutation is a late event occurring probably during tumor progression in AFB(1) and HHBV induced hepatocarcinogenesis in the tree shrew. This report is the first example of an experimental animal model where combination of human HBV and AFB(1)-induced HCCs demonstrate p53 expression.