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

Gene. 2000 Jun 13;251(1):73-80. doi: 10.1016/s0378-1119(00)00183-9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aflatoxin B1 / toxicity*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Carcinoma, Hepatocellular / chemically induced
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / virology
  • Cloning, Molecular
  • DNA Mutational Analysis
  • DNA, Complementary / chemistry
  • DNA, Complementary / genetics
  • Disease Models, Animal
  • Genes, Tumor Suppressor / genetics
  • Hepatitis B / virology*
  • Hepatitis B virus
  • Liver / metabolism
  • Liver / pathology
  • Liver Neoplasms / chemically induced
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / 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*

Substances

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

Associated data

  • GENBANK/AF175893