Hepatitis B virus replication causes oxidative stress in HepAD38 liver cells.
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).


CONCLUSIONS
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.
Severi
Tamara
T
Department of Hepatology, University Hospital Gasthuisberg, Leuven, Belgium.
Ying
Chunxiao
C
Vermeesch
Joris Robert
JR
Cassiman
David
D
Cnops
Lieselotte
L
Verslype
Chris
C
Fevery
Johan
J
Arckens
Lutgarde
L
Neyts
Johan
J
van Pelt
Jos F
JF
D015415:Biomarkers / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015967:Gene Expression Regulation, Viral; D006515:Hepatitis B virus / Q000235:genetics*; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007621:Karyotyping; D008113:Liver Neoplasms / Q000378:metabolism*; D018384:Oxidative Stress; D012367:RNA, Viral / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D014779:Virus Replication
D015415:Biomarkers; D012367:RNA, Viral