Oxidative Damage Is Increased in Human Liver Tissue Adjacent to Hepatocellular Carcinoma
post-template-default,single,single-post,postid-19129,single-format-standard,bridge-core-1.0.4,ajax_fade,page_not_loaded,,qode-title-hidden,qode-theme-ver-18.0.9,qode-theme-bridge,qode_header_in_grid,wpb-js-composer js-comp-ver-5.7,vc_responsive

Oxidative Damage Is Increased in Human Liver Tissue Adjacent to Hepatocellular Carcinoma

发表时间:2004-12-16 17:11


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 3 T:A transversions.TheselesionscanbeenzymaticallyrepairedmainlybyhumanMutThomolog 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 enzymesintumor(tu)andcorrespondingadjacentnontumor(ntu)livertissueof23patients 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/ ? g DNA) as compared to tu tissue (median, 52 fmol/ ? g 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 poly- merase 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 contributetohumanhepatocarcinogenesis.TheroleofDNArepairenzymesappearstobeof reactive rather than causative manner.