title: Interactions between hepatitis B virus and aflatoxin B(1): effects on p53 induction in HepaRG cells.
abstract: Infection by hepatitis B virus (HBV) and dietary exposure to aflatoxin B(1) (AFB(1)) are the main risk factors for the development of chronic liver disease and hepatocellular carcinoma (HCC). How these factors cooperate is still largely unknown. AFB(1) activation leads to DNA adduction and mutagenesis, with a specific mutation at codon 249 in TP53 (p.R249S). So far, only limited studies have addressed the effects of AFB(1) on HBV replication. We have analysed the effects of both risk factors on p53 induction during HBV infection in HepaRG, a cell line with hepatocyte-like morphology that metabolizes AFB(1) and supports HBV infection. Exposure to AFB(1) up to 5 µM induced a downregulation of HBV replication after 48 h, as measured by a decrease in viral antigens in the culture medium (HBsAg, HBeAg and large envelope protein) and in intracellular levels of HBV transcripts, DNA and HBsAg. Conversely, HBV infection did not significantly modify AFB(1)-DNA adduct formation or repair as assessed by immunodot-blot assay, and the induction of p53 in response to AFB(1) was similar in infected and non-infected HepaRG cells. Overall, our results suggest that AFB(1) exposure decreases HBV replication, whereas DNA damage by AFB(1) and subsequent p53 induction is not affected by the presence of the virus. Thus, in HepaRG cell line, AFB(1) and HBV do not cooperate to increase DNA damage by AFB(1). Further studies on the effects of both factors in a context of chronicity are needed to better understand synergistic effects.
authors: International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France.|INSERM U1052, 151 cours Albert Thomas, 69424 Lyon Cedex 03, France.
authors: Myriam
authors: M
authors: Lereau
authors: International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France.
authors: Doriane
authors: D
authors: Gouas
authors: International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France.
authors: Stéphanie
authors: S
authors: Villar
authors: Department of Cancer Biology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, 1500 East Duarte Road, Duarte, CA 91010-3000, USA.
authors: Ahmad
authors: A
authors: Besaratinia
authors: International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France.
authors: Agnès
authors: A
authors: Hautefeuille
authors: INSERM U1052, 151 cours Albert Thomas, 69424 Lyon Cedex 03, France.
authors: Pascale
authors: P
authors: Berthillon
authors: International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France.
authors: Ghislaine
authors: G
authors: Martel-Planche
authors: International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France.
authors: André
authors: A
authors: Nogueira da Costa
authors: International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France.
authors: Sandra
authors: S
authors: Ortiz-Cuaran
authors: INSERM U1052, 151 cours Albert Thomas, 69424 Lyon Cedex 03, France.
authors: Olivier
authors: O
authors: Hantz
authors: Department of Cancer Biology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, 1500 East Duarte Road, Duarte, CA 91010-3000, USA.
authors: Gerd P
authors: GP
authors: Pfeifer
authors: International Center for Research and Training, Hospital AC Camargo, Rua Pirapitinguí 204, São Paulo SP 01508 - 020, Brazil.|International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France.
authors: Pierre
authors: P
authors: Hainaut
authors: INSERM U1052, 151 cours Albert Thomas, 69424 Lyon Cedex 03, France.
authors: Isabelle
authors: I
authors: Chemin
mesh_terms: D016604:Aflatoxin B1 / Q000633:toxicity*; D002460:Cell Line; D004249:DNA Damage; D006515:Hepatitis B virus / Q000187:drug effects / Q000472:pathogenicity*; D022781:Hepatocytes / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D016159:Tumor Suppressor Protein p53; D016604:Aflatoxin B1