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

Jianjia Su,Dingrui Huang,Guohua Huang,Ruiqi Yan,Guozhong Qin,Chun Yang,Prabhakar D Lotlikar

doi:10.1038/emm.1997.27

Jianjia Su, Dingrui Huang + Show 5 more

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https://doi.org/10.1038/emm.1997.27

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Journal: Experimental and Molecular Medicine	Publication Date: Sep 1, 1997
Citations: 3	License type: cc-by

Affiliation: Temple University

Abstract

Using tree shrew as an animal model, our previous studies have demonstrated synergistic effects ofaflatoxin B₁(AFB₁) 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 AFB₁ 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 AFB₁ with HHBV infection and 2/3 animals with HCCs (66.7%) induced by AFB₁ alone expressed the p53 protein. Out of 18 HCCs examined, expression of p53 protein was observed in 9/10 moderately and poorly differ-entiated HCCs (90.0%). 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 AFB₁ and HHBV induced hepa-tocarcinogenesis in the tree shrew. This report is the first example of an experimental animal model where combination of human HBV and AFB₁-induced HCCs demonstrate p53 expression.

Highlights

Hepatocellular carcinoma (HCC) is one of the world’s most common cancers, occurring especially in Africa and South-East Asia (Beasley, 1982; Parkin et al, 1988)
On the basis of their results, we investigated the hepatocarcinogenesis of aflatoxin B1 (AFB1) and human hepatitis B virus (HBV) (HHBV) in this species (Yan et al, 1996a, 1996b)
The results indicated that the HCC incidence was significantly higher in the tree shrews exposed to both human hepatitis B virus (HHBV) and AFB1 than in those which

Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the world’s most common cancers, occurring especially in Africa and South-East Asia (Beasley, 1982; Parkin et al, 1988). Mutation of G to T transversion at codon 249 position 3 of p53 gene has been detected in human HCCs associated with high exposure to AFB1 in Africa and in Qidong, China (Bressac et al, 1991; Hsu et al, 1991; Scorsone et al, 1992). The frequency of p53 mutations in HCCs in different studies are variable from 18% to 67% These p53 mutations are more frequent in HBV-infected HCC patients exposed to AFB1 (Bressac et al, 1991; Goldblum et al, 1993; Hosono et al, 1993; Hsu et al, 1991; Livni et al, 1995; Nagao et al, 1995; Scorsone et al, 1992)

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