Oxidative damage is increased in human liver tissue adjacent to hepatocellular carcinoma

被引:98
作者
Jüngst, C
Cheng, B
Gehrke, R
Schmitz, V
Nischalke, HD
Ramakers, J
Schramel, P
Schirmacher, P
Sauerbruch, T
Caselmann, WH
机构
[1] Univ Bonn, Dept Internal Med 1, D-5300 Bonn, Germany
[2] Max Planck Inst Biochem, Dept Virus Res, D-82152 Martinsried, Germany
[3] GSF, Natl Res Ctr Environm, Neuherberg, Germany
[4] Hlth Inst Ecol Chem, Neuherberg, Germany
[5] Univ Cologne, Inst Pathol, D-5000 Cologne, Germany
关键词
D O I
10.1002/hep.20241
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Accumulation of genetic alterations in hepatocarcinogenesis is closely associated with chronic inflammatory liver disease. 8-oxo-2'-deoxyguanosine (8-oxo-dG), the major pro-mutagenic 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/mug DNA) as compared to tu tissue (median, 52 fmol/mug 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.
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页码:1663 / 1672
页数:10
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