title: 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.affiliation: Bioscience Research Division, Korea Research Institute of Bioscience and Biotechnology, Taejon, South Korea.
authors.forename: U S
authors.initials: US
authors.lastname: Park
authors.forename: J J
authors.initials: JJ
authors.lastname: Su
authors.forename: K C
authors.initials: KC
authors.lastname: Ban
authors.forename: L
authors.initials: L
authors.lastname: Qin
authors.forename: E H
authors.initials: EH
authors.lastname: Lee
authors.forename: Y I
authors.initials: YI
authors.lastname: Lee
mesh_terms: D016604:Aflatoxin B1 / Q000633:toxicity*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000235:genetics* / Q000821:virology; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D004195:Disease Models, Animal; D016147:Genes, Tumor Suppressor / Q000235:genetics; D006509:Hepatitis B / Q000821:virology*; D006515:Hepatitis B virus; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000821:virology; D008969:Molecular Sequence Data; D009154:Mutation; D017354:Point Mutation; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D014418:Tupaiidae / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D016159:Tumor Suppressor Protein p53; D016604:Aflatoxin B1