POINT MUTATIONS OF THE P53 GENE, HUMAN HEPATOCELLULAR-CARCINOMA AND AFLATOXINS

The tumor suppressor p53 exerts important protective functions towards DNA-damaging agents. Its inactivation by allelic deletions or point m utations within the P53 gene as well as complex formation of wildtype p53 with cellular or viral proteins is a common and crucial event in c arcinogenesis. Mutations increase the half-life of the p53 protein all owing the immunohistochemical detection and anti-p53 antibody formatio n. Distinct G to T point mutations in codon 249 leading to a substitut ion of the basic amino acid arginine by the neutral amino acid serin a re responsible for the altered functionality of the mutant gene produc t and were originally identified in 8 of 16 Chinese and 5 of 10 Africa n HCC patients. Both groups are frequently exposed to mycotoxin contam inations of their food. Today an average P53 gene mutation rate of 25% is assumed for high-aflatoxin B-1-exposure regions. This is double th e rate observed in low-aflatoxin B-1-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 indu ce 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 B-1 exposure.