title: Absence of mutations in the p53 tumor suppressor gene in woodchuck hepatocellular carcinomas associated with hepadnavirus infection and intake of aflatoxin B1.
abstract: Infection with hepadnaviruses and exposure to aflatoxin B1 (AFB1) are considered major risk factors in the development of hepatocellular carcinoma (HCC) in humans and in animals. A high rate of mutations in the p53 tumor suppressor gene in hepatocellular carcinomas of predominantly hepatitis B virus (HBV) carrier patients has been recently related to dietary aflatoxin. Another member of the hepadnavirus family, the woodchuck hepatitis virus (WHV), infects woodchucks in a manner similar to that of HBV in humans. Therefore, it was of particular interest to determine whether the p53 gene in woodchuck HCCs associated with hepadnavirus infection and with exposure to AFB1 is affected in the same manner as in human HCCs. By direct PCR-sequencing, we analyzed exons 4-9 of the p53 gene in 13 HCCs from 12 woodchucks (two uninfected, ten WHV carriers). Six WHV carrier and two uninfected woodchucks were treated with AFB1. None of the analyzed HCC samples exhibited mutations, either in p53 gene exons 4-9, or in splicing donor-acceptor sites. The present data are consistent with our previous study that indicated a low rate of p53 mutations in HCCs of AFB1-treated ground squirrels, either infected or not infected with ground squirrel hepatitis virus, and in WHV carrier woodchucks not exposed to AFB1. Overall, our findings indicate that in woodchucks and in ground squirrels exposure to aflatoxin may affect the development of p53 mutations less than in humans.
authors.affiliation: Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, CA 94305, USA.
authors.forename: M
authors.initials: M
authors.lastname: Rivkina
authors.forename: P J
authors.initials: PJ
authors.lastname: Cote
authors.forename: W S
authors.initials: WS
authors.lastname: Robinson
authors.forename: B C
authors.initials: BC
authors.lastname: Tennant
authors.forename: P L
authors.initials: PL
authors.lastname: Marion
mesh_terms: D016604:Aflatoxin B1 / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000235:genetics; D004279:DNA, Viral / Q000032:analysis; D005091:Exons; D016158:Genes, p53; D006509:Hepatitis B / Q000150:complications*; D017919:Hepatitis B Virus, Woodchuck; D008113:Liver Neoplasms / Q000209:etiology* / Q000235:genetics; D008392:Marmota; D009154:Mutation
chemical_list: D002273:Carcinogens; D004279:DNA, Viral; D016604:Aflatoxin B1