Abstract:
BACKGROUND/AIMS:Transgenic mice overexpressing hepatitis B x protein (HBx) show an increased susceptibility to mutations if exposed to mutagens. Also involved in HBx signalling, reactive oxygen intermediates (ROI) can induce DNA adducts such as 8-hydroxy-2'-deoxyguanosine that can in turn lead to G/T transversion mutations. Therefore, we investigated whether HBx expression increases the level of the mutational precursor 8-hydroxy-2'-deoxyguanosine in hepatocellular DNA. METHODS:8-hydroxy-2'-deoxyguanosine concentrations of DNA hydrolysates of HBx protein expressing HepG2 cells and livers of HBx transgenic mouse lines were determined electrochemically after HPLC fractionation. RESULTS:8-hydroxy-2'-deoxyguanosine concentrations in genomic DNA of HBx protein expressing cell lines correlated with the factor of transactivation. The 8-hydroxy-2'-deoxyguanosine levels were reduced after incubation of HBx recombinant cell lines with 0.1 or 1 mM of the antioxidant N-acetylcysteine. Hepatic 8-hydroxy-2'-deoxyguanosine concentrations in DNA of old transgenic mice were significantly, i.e. twofold, (p < 0.01) increased as compared to those of old nontransgenic or young transgenic controls and of control mice expressing a second HBV transactivator (MHBs(t76)). CONCLUSION:HBx expression results in elevated DNA adduct levels. This could reflect a direct inhibitory interaction of HBx with cellular repair mechanisms. Alternatively, this may be an effect of an increased generation of reactive oxygen intermediates through HBx.
journal_name
Digestionjournal_title
Digestionauthors
Gehrke R,Brauchle MA,Reifenberg K,Hildt E,Gruetzner U,Schmitz V,Schlicht HJ,Hofschneider PH,Caselmann WH,Rabe Cdoi
10.1159/000080930subject
Has Abstractpub_date
2004-01-01 00:00:00pages
117-26issue
2eissn
0012-2823issn
1421-9867pii
80930journal_volume
70pub_type
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