The p53 tumor suppressor gene is commonly mutated in human hepatocellular carcinoma (HCC).
The most frequent mutation in HCC in populations exposed to a high dietary intake of aflatoxin B1 (AFB1) is an AGGarg-AGTser missense mutation in codon 249 of the p53 gene.
We analyzed HCCs from Monterrey, Mexico, for the codon 249ser hotspot mutation.
We also analyzed the serum AFB1-albumin adduct levels of the donors and family members to measure the current AFB1 exposure in this population.
Moreover, the presence of hepatitis B and/or C viral infection (HBV or HCV) was analyzed serologically in the patients.
Tumor cells were microdissected from tissue sections and exon 7 p53 sequences were amplified by polymerase chain reaction from genomic DNA and sequenced directly.
The serological tests for anti-p53 antibodies, HBV or HCV were done by ELISA.
Immunohistochemical analysis of p53 protein was done using a polyclonal rabbit antiserum (CM-1).
Eight of 21 cases were positive by p53 immunohistochemistry.
Of the 16 cases sequenced for exon 7 of p53 three codon 249 AGGarg-AGTser mutations were found.
Serum antibodies recognizing p53 protein were found in one of 18 patients.
Positive serology for HBV and/or HCV was found in 12 of 20 cases.
The serum AFB1-albumin adduct levels in this population ranged from 0.54 to 4.64 pmol aflatoxin/mg albumin.
These results indicate that dietary AFB1 and hepatitis viruses are etiological agents in the molecular pathogenesis of HCC in th...
Mots-clés Pascal : Aflatoxine B1, Mutation, Point chaud, Carcinome hépatocellulaire, Gène suppresseur tumeur, Hépatite virale B, Virose, Infection, Hépatite virale C, Chronique, Homme, Mexique, Amérique Centrale, Amérique, Aliment, Contamination, Epidémiologie, Pathogénie, Appareil digestif pathologie, Foie pathologie, Tumeur maligne, Biologie moléculaire, Gène p53
Mots-clés Pascal anglais : Aflatoxin B1, Mutation, Hot spot, Liver cell carcinoma, Tumor suppressor gene, Viral hepatitis B, Viral disease, Infection, Viral hepatitis C, Chronic, Human, Mexico, Central America, America, Food, Contamination, Epidemiology, Pathogenesis, Digestive diseases, Hepatic disease, Malignant tumor, Molecular biology, p53 gene
Notice produite par :
Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 96-0271315
Code Inist : 002B13C01. Création : 199608.