Accumulation of genetic alterations in hepatocarcinogenesis is closely associated with chronic inflammatory
liver disease.
8-oxo-2'-deoxyguanosine (8-oxo-dG), the major promutagenic
DNA adduct caused by
reactive oxygen species (ROS), leads to G:C --> T:A transversions. These lesions can be enzymatically repaired mainly by human MutT homolog 1 (hMTH1), human 8-oxo-guanine
DNA glycosylase (hOGG1) and human MutY homolog (hMYH). The aim of this study was to evaluate the extent of oxidative damage and its dependence on the cellular antioxidative capacity and the expression of specific
DNA repair enzymes in
tumor (tu) and corresponding adjacent nontumor (ntu) liver tissue of 23 patients with histologically confirmed
hepatocellular carcinoma.
8-oxo-dG levels, as detected by high-pressure liquid chromatography with electrochemical detection, were significantly (P =.003) elevated in ntu tissue (median, 129 fmol/microg
DNA) as compared to tu tissue (median, 52 fmol/microg
DNA), and were closely associated with inflammatory infiltration. In ntu tissue, the hepatic
iron concentration and
malondialdehyde levels were significantly (P =.001) higher as compared to tu tissue.
Glutathione content,
glutathione peroxidase activity and
manganese superoxide dismutase messenger RNA (
mRNA) expression did not show statistical differences between ntu and tu tissue. Real-time reverse transcription polymerase chain reaction revealed in tu tissue significantly (P =.014) higher hMTH1
mRNA expression compared to ntu tissue. In contrast, hMYH
mRNA expression was significantly (P <.05) higher in ntu tissue. No difference in hOGG1
mRNA expression was seen between tu and ntu. In conclusion, these data suggest that ROS generated by chronic
inflammation contribute to human hepatocarcinogenesis. The role of
DNA repair enzymes appears to be of reactive rather than causative manner.