Altered DNA mutation spectrum in aflatoxin b1-treated transgenic mice that express the hepatitis B virus x protein

J Virol. 2002 Nov;76(22):11770-4. doi: 10.1128/jvi.76.22.11770-11774.2002.


Humans chronically infected with hepatitis B virus (HBV) are at further risk of liver cancer upon exposure to dietary aflatoxin B1 (AFB1), a carcinogenic product of the mold Aspergillus flavus. For the present study, we utilized double-transgenic mice (ATX mice) that express the HBV X protein (HBx) and possess a bacteriophage lambda transgene to evaluate the in vivo effect of HBx expression on AFB1-induced DNA mutations. The expression of HBx correlated with a 24% increase in mutation frequency overall and an approximately twofold increase in the incidence of G/C-to-T/A transversion mutations following AFB1 exposure. These results are consistent with a model in which expression of HBx during chronic HBV infection may contribute to the development of hepatocellular carcinoma following exposure to environmental carcinogens.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aflatoxin B1 / toxicity*
  • Animals
  • Bacteriophage lambda / genetics
  • Carcinoma, Hepatocellular / etiology
  • DNA / metabolism*
  • Female
  • Hepatitis B, Chronic / complications
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Mice, Transgenic
  • Mutation*
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism*
  • Transgenes
  • Viral Regulatory and Accessory Proteins


  • Trans-Activators
  • Viral Regulatory and Accessory Proteins
  • hepatitis B virus X protein
  • DNA
  • Aflatoxin B1