ABSENCE OF P53 MUTATION AT CODON-249 IN DUCK HEPATOCELLULAR CARCINOMAS FROM THE HIGH-INCIDENCE AREA OF QIDONG (CHINA)

Dietary aflatoxin and hepatitis B virus infection may play a role in g enerating the p53 tumor suppressor gene codon 249 hotspot mutation fou nd in human hepatocellular carcinomas (HCCs) from Qidong (China) and s outhern Africa. No data are available on the HCC site-specific mutatio n of the p53 gene in hepadnavirus-infected animals exposed to AFB(1). We have searched for the presence of p53 gene codon 249 mutations in b oth duck hepatitis B virus (DHBV) positive and negative HCCs of domest ic ducks from Qidong, where the human p53 hotspot is so prevalent, as well as in duck HCCs experimentally induced by AFB(1). Direct sequenci ng of DNA amplification products encompassing p53 codon 249 did not re veal any mutations in 11 HCCs from Qidong ducks, regardless of the sta tus of DHBV infection. In addition no mutation was detected in four HC Cs from AFB(1)-treated ducks. This contrasts with the human data; howe ver, in humans, the mutation and the preferential binding of AFB(1) to codon 249 occurs at the third nucleotide G, while in duck, the codon 249 lacks this G residue. The DNA sequence of adjacent codons is also different in the two species even though the amino acid sequence is id entical. This may explain the low frequency of mutation we have observ ed. In addition, species differences in metabolism and DNA repair coul d influence the occurrence of codon 249 mutations.