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Hepatitis B virus replication causes oxidative stress in HepAD38 liver cells

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Abstract

We used human hepatoma HepAD38 cells, in which HBV production is under the control of a tetracycline-regulated promotor, to investigate changes induced in the host cell by HBV replication that could contribute to malignant transformation. Parameters of oxidative stress (malondialdehyde, glutathione) and cell proliferation were determined at different times after induction (0–96 h). In HBV-producing cells, the redox status peaked at 72 h. cDNA micro array analysis at 72 h post induction revealed 3 groups of genes that were up-regulated by HBV: (i) heat shock proteins, (ii) oxidative and metabolic stress and (iii) growth and apoptosis related genes. Continuous HBV production did not accelerate karyotypic changes in cells cultured for 4 months (18 passages). In conclusion: HBV replication modulates host gene expression and induces oxidative stress. In this HepAD38 model early events (0–4 days) in the host cell after induction of HBV replication can be studied under strictly defined conditions.

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Abbreviations

FCS:

foetal calf serum

GSH:

glutathione

GSSG:

oxidized glutathione

HCC:

hepatocellular carcinoma

MDA:

malondialdehyde

MTT:

3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide

ROS:

reactive oxygen species, tet, tetracycline

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Authors and Affiliations

  1. Department of Hepatology, University Hospital Gasthuisberg, Leuven, Belgium

    Tamara Severi, David Cassiman, Chris Verslype, Johan Fevery & Jos F. van Pelt PhD Ing

  2. Laboratory of Virology and Experimental Chemotherapy, Rega Institute, Faculty of Medicine, Leuven, Belgium

    Chunxiao Ying & Johan Neyts

  3. Department of Human Genetics, Faculty of Medicine, Leuven, Belgium

    Joris Robert Vermeesch

  4. Laboratory of Neuroplasticity and Neuroproteomics, Faculty of Science, Leuven, Belgium

    Lieselotte Cnops & Lutgarde Arckens

  5. Laboratory of Hepatology, University Hospital Gasthuisberg, O&N Building Bus 703, Herestraat 49, B3000, Leuven, Belgium

    Jos F. van Pelt PhD Ing

Authors
  1. Tamara Severi
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  2. Chunxiao Ying
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  3. Joris Robert Vermeesch
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  4. David Cassiman
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  5. Lieselotte Cnops
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  6. Chris Verslype
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  7. Johan Fevery
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  8. Lutgarde Arckens
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  9. Johan Neyts
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  10. Jos F. van Pelt PhD Ing
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Corresponding author

Correspondence to Jos F. van Pelt PhD Ing.

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Severi, T., Ying, C., Vermeesch, J.R. et al. Hepatitis B virus replication causes oxidative stress in HepAD38 liver cells. Mol Cell Biochem 290, 79–85 (2006). https://doi.org/10.1007/s11010-006-9167-x

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  • DOI: https://doi.org/10.1007/s11010-006-9167-x

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