Decreased oxidative DNA damage and accelerated cell turnover in woodchuck hepatitis virus infected liver.
Infection of newborn woodchucks with woodchuck hepatitis virus (WHV) results in hepatocellular carcinoma (HCC). Since oxidative damage may be carcinogenic, we investigated the relationship between WHV infection and oxidative damage to hepatic lipids and DNA. Eastern woodchucks were infected with WHV. Hepatic lipid peroxidation was assessed in vitro in isolated hepatocytes by thiobarbituric acid reactive substances (TBARS). Oxidative DNA damage was assessed in vivo in snap-frozen livers by 8-hydroxy-2'-deoxyguanosine (8-OH-dG). The proliferation index (PI) and apoptotic index (AI) were also determined. WHV infection was associated with increased hepatic lipid peroxidation (0.51+/-0.04 nmols TBARS per mg protein for WHV+ hepatocytes vs. 0.38+/-0.04 for WHV negative controls, P<0.01). In contrast, the WHV+ livers exhibited less oxidative DNA damage than uninfected controls (11+/-5 vs. 38+/-8 8-OH-dG/10(6) dG, P<0.02). In WHV-infected animals PI and AI were increased, by >20-fold. We conclude that WHV infection is associated with increased in vitro lipid peroxidation and decreased in vivo oxidative DNA damage. The increased PI and AI in the WHV+livers suggest that rapid cell turnover dilutes 8-OH-dG concentration.
O'Gorman
Molly A.
MA
Department of Pediatrics, Division of Pediatric Gastroenterology and Nutrition, Johns Hopkins Medical Institutions, Johns Hopkins University School of Medicine, 600 N. Wolfe Street-Brady 320, 21287, Baltimore, MD, USA
Sharma
Savitri
S
Groopman
John D.
JD
Tennant
Bud C.
BC
Tochkov
Ilia A.
IA
Schwarz
Kathleen B.
KB