Altered DNA mutation spectrum in aflatoxin b1-treated transgenic mice that express the hepatitis B virus x protein.
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.
Madden
Charles R
CR
Department of Molecular Virology and Microbiology. Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA.
Finegold
Milton J
MJ
Slagle
Betty L
BL
D016604:Aflatoxin B1 / Q000633:toxicity*; D000818:Animals; D010582:Bacteriophage lambda / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000209:etiology; D004247:DNA / Q000378:metabolism*; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D009154:Mutation; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*; D019076:Transgenes; D054334:Viral Regulatory and Accessory Proteins
D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D004247:DNA; D016604:Aflatoxin B1