title: Point mutations of the P53 gene, human hepatocellular carcinoma and aflatoxins.
abstract: The tumor suppressor p53 exerts important protective functions towards DNA-damaging agents. Its inactivation by allelic deletions or point mutations within the P53 gene as well as complex formation of wildtype p53 with cellular or viral proteins is a common and crucial event in carcinogenesis. Mutations increase the half-life of the p53 protein allowing the immunohistochemical detection and anti-p53 antibody formation. Distinct G to T point mutations in codon 249 leading to a substitution of the basic amino acid arginine by the neutral amino acid serine are responsible for the altered functionality of the mutant gene product and were originally identified in 8 of 16 Chinese and 5 of 10 African HCC patients. Both groups are frequently exposed to mycotoxin contaminations of their food. Today an average P53 gene mutation rate of 25% is assumed for high-aflatoxin B1-exposure regions. This is double the rate observed in low-aflatoxin B1-exposure countries. Although many HCC patients displaying P53 mutations also suffer from HBV infection, which itself can lead to rearrangements of P53 coding regions or induce the synthesis of viral proteins possibly interacting with p53, the specific G to T transversion within codon 249 of the P53 gene seems to directly reflect the extent of aflatoxin B1 exposure.
authors.affiliation: Department of Medicine II, Klinikum Grosshadern, University of Munich, Germany.
authors.forename: A L
authors.initials: AL
authors.lastname: Gerbes
authors.forename: W H
authors.initials: WH
authors.lastname: Caselmann
mesh_terms: D000348:Aflatoxins / Q000009:adverse effects*; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D004032:Diet / Q000009:adverse effects; D004781:Environmental Exposure; D016158:Genes, p53 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology* / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*
chemical_list: D000348:Aflatoxins; D004273:DNA, Neoplasm