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

作者：DUFLOT A^*; HOLLSTEIN M; MEHROTRA R; TREPO C; MONTESANO R; COVA L

来源：Carcinogenesis, 1994, 15(7): 1353-1357.

DOI：10.1093/carcin/15.7.1353

Dietary aflatoxin and hepatitis B virus infection may play a role in generating the p53 tumor suppressor gene codon 249 hotspot mutation found in human hepatocellular carcinomas (HCCs) from Qidong (China) and southern Africa. No data are available on the HCC site-specific mutation 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 both duck hepatitis B virus (DHBV) positive and negative HCCs of domestic ducks from Qidong, where the human p53 hotspot is so prevalent, as well as in duck HCCs experimentally induced by AFB(1). Direct sequencing of DNA amplification products encompassing p53 codon 249 did not reveal any mutations in 11 HCCs from Qidong ducks, regardless of the status of DHBV infection. In addition no mutation was detected in four HCCs from AFB(1)-treated ducks. This contrasts with the human data; however, 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 identical. This may explain the low frequency of mutation we have observed. In addition, species differences in metabolism and DNA repair could influence the occurrence of codon 249 mutations.

• 出版日期1994-7