19 research outputs found
Seasonal Variation in TP53 R249S-Mutated Serum DNA with Aflatoxin Exposure and Hepatitis B Virus Infection
Background: Chronic hepatitis B virus (HBV) infection and dietary aflatoxin B1 (AFB1) exposure are etiological factors for hepatocellular carcinoma (HCC) in countries with hot, humid climates. HCC often harbors a TP53 (tumor protein p53) mutation at codon 249 (R249S). In chronic carriers, 1762T/1764A mutations in the HBV X gene are associated with increased HCC risk. Both mutations have been detected in circulating cell-free DNA (CFDNA) from asymptomatic HBV carriers
Synergism between hepatitis B virus and aflatoxin B1 during hepatocarcinogenesis : effects on p53 induction
Dans les pays dâAfrique Sub-Saharienne et dâAsie du Sud-Est, lâinfection chronique par le virus de lâhĂ©patite B (VHB) et lâexposition Ă lâaflatoxine B1 (AFB1) ont un rĂŽle synergique dans le dĂ©veloppement du carcinome hĂ©patocellulaire (CHC). Cependant les mĂ©canismes impliquĂ©s ne sont pas Ă©lucidĂ©s Ă ce jour. Le VHB est un petit virus Ă ADN qui induit diffĂ©rentes maladies du foie allant du portage asymptomatique au CHC. LâAFB1 est une mycotoxine qui contamine la nourriture. AprĂšs activation en Ă©poxyde, elle forme des adduits Ă lâADN puis des mutations, dont la mutation au codon 249 du gĂšne suppresseur de tumeur TP53 (AGG â AGT, mutation R249S). Nous avons utilisĂ© les caractĂ©ristiques uniques de la lignĂ©e cellulaire HepaRG pour Ă©tudier les interactions entre le VHB et lâAFB1 : ces cellules se diffĂ©rencient in vitro en hĂ©patocytes qui mĂ©tabolisent lâAFB1 et peuvent ĂȘtre infectĂ©s par le VHB. Nous avons montrĂ© que lâAFB1 induit une rĂ©ponse de p53 dose-dĂ©pendante et agit comme un agent antiviral en rĂ©primant la production de particules virales aprĂšs 48h dâexposition. Dâautre part, lâinfection par le VHB nâa montrĂ© aucun effet sur la formation ou la rĂ©paration des adduits. De la rĂ©paration et de la prolifĂ©ration cellulaire ont Ă©tĂ© observĂ©es suite au traitement Ă lâAFB1, suggĂ©rant la faisabilitĂ© de lâĂ©tude de mutations dans ce systĂšme, dont R249S. Ces rĂ©sultats suggĂšrent que lâAFB1 attĂ©nue lâhĂ©patite chronique tout en maintenant les hĂ©patocytes sous intense pression mutagĂšne, ce qui favoriserait la progression vers le CHCIn sub-Saharan Africa and South-East Asia, chronic infection by hepatitis B virus (HBV) and exposure to aflatoxin B1 (AFB1) play a synergic role in the development of hepatocellular carcinoma (HCC). However mechanisms are still largely unknown. HBV is a small DNA virus which induces different liver diseases from asymptomatic carriage to HCC. AFB1 is a mycotoxin which contaminates food. After activation into an epoxide, it forms DNA adducts and mutations, such as R249S mutation at codon 249 in tumor suppressor TP53 gene (AGG â AGT). We have taken advantage of the unique features of the cell line HepaRG to investigate interactions between both risk factors: cells differentiate in vitro into hepatocytes which metabolize AFB1 and can be infected by HBV. We have shown that AFB1 induces a dose-dependent p53 response and act as an antiviral agent by repressing production of HBV particles after 48 hours of exposure. Nevertheless HBV infection had no effect on adduct formation or repair. Moreover DNA synthesis activity associated to DNA repair and cell proliferation were observed following AFB1 treatment, suggesting the feasibility of mutation research in this model, especially R249S. Overall these results suggest that AFB1 may attenuate HBV chronic hepatitis while maintaining hepatocytes under intense mutagenic pressure, thus enhancing the progression towards HC
Development of sensitive probes for direct and labelless detection of nucleic acids by electrochemistry : Application to hepatitis C virus genotyping
International audienc
Metabolomic profiling during the differentiation of human induced pluripotent stem cells into hepatocyte-like cells
International audienc
Polythiol probes for sensitive detection of nucleic acids : Application to hepatitis C virus genotyping
International audienc
Characterization of liver zonationâlike transcriptomic patterns in HLCs derived from hiPSCs in a microfluidic biochip environment
International audienc
Polythiol probes for sensitive detection of nucleic acids : Application to hepatitis C virus genotyping
International audienc