Mutations in the p53 tumor suppressor gene in tree shrew hepatocellular carcinoma associated with hepatitis B virus infection and intake of aflatoxin B1.

Abstract

Infection with hepadnaviruses and exposure to aflatoxin B1 (AFB1) are considered to be major risk factors in the development of hepatocellular carcinoma (HCC) in humans. A high rate of p53 mutations at codon 249 has been reported in these tumors. The tree shrew (Tupaia belangeri chinensis) is a useful animal model for the development of HCC after human hepatitis B virus (HBV) infection or AFB1 treatment. Therefore, it was of particular interest to determine whether the p53 gene in tree shrew HCCs associated with HBV infection and/or with exposure to AFB1 is affected in the same manner as in human HCCs. We determined the tree shrew p53 wild-type nucleotide sequences by RT-PCR and automatic DNA-sequencing. Tree shrew wild-type p53 sequence showed 91.7 and 93.4% homologies with human p53 nucleotide and amino acids sequences, respectively, while it showed 77.2 and 73.7% homologies in mice. One HCC and normal liver tissue from AFB1 treated and one HCC from AFB1- and HBV-treated tree shrew showed no change in p53 sequences, while three HCCs from AFB1- and HBV-treated tree shrews showed point mutations in p53 sequences. One HCC showed point mutations at codon 275, which is on the DNA-binding domain of p53 gene, which might be a cause of gain-of-function during the development of HCC. As a result, our finding indicates that tree shrews exposed to AFB1 and/or HBV had neither codon 249 mutations nor significant levels of other mutations in the p53 gene, as is the case with humans.

• Authors: U S Park, J J Su, K C Ban, L Qin, E H Lee, Y I Lee
• Journal: Gene (Gene) Vol. 251 Issue 1 Pg. 73-80 (Jun 13 2000) ISSN: 0378-1119 [Print] Netherlands
• PMID: 10863098 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Complementary
• Tumor Suppressor Protein p53
• Aflatoxin B1

Topics

• Aflatoxin B1 (toxicity)
• Amino Acid Sequence
• Animals
• Base Sequence
• Carcinoma, Hepatocellular (chemically induced, genetics, virology)
• Cloning, Molecular
• DNA Mutational Analysis
• DNA, Complementary (chemistry, genetics)
• Disease Models, Animal
• Genes, Tumor Suppressor (genetics)
• Hepatitis B (virology)
• Hepatitis B virus
• Liver (metabolism, pathology)
• Liver Neoplasms (chemically induced, genetics, virology)
• Molecular Sequence Data
• Mutation
• Point Mutation
• Sequence Alignment
• Sequence Analysis, DNA
• Sequence Homology, Amino Acid
• Sequence Homology, Nucleic Acid
• Tumor Suppressor Protein p53 (genetics)
• Tupaiidae (genetics)