title: Oxidative stress-induced 1, N6-ethenodeoxyadenosine adduct formation             contributes to hepatocarcinogenesis.
abstract: Numerous studies have found that oxidative stress-derived 1, N6-ethenodeoxyadenosine             (ε-dA) can act as a driving force towards hepatocellular carcinoma (HCC) in cancer-prone             liver diseases. The aim of the present study was to determine the oxidative stress             status and the occurrence of ε-dA in HCC and adjacent non-tumor liver tissue,             and to clarify whether the occurrence of ε-dA is related to liver inflammatory             activity, fibrosis and mutant p53 expression. Oxidative stress-related parameters             were examined in tumor and (or) non-tumor liver tissues of 32 patients with HCC.             ε-dA, mutant p53 and proliferating cell nuclear antigen (PCNA) were immunohistochemically             investigated in control, HCC and non-tumor liver tissues. The total antioxidant             capacity and total superoxide dismutase activity of HCC tissues were lower compared             to those of non-tumor tissues (P<0.05 vs. P<0.001). The prevalence of ε-dA             in HCC was significantly higher compared to control (P<0.0001) and non-tumor             liver tissues (P<0.001). A significant correlation between the positive rate             of ε-dA and mutant p53 was observed (r=0.5162, P<0.01). The positive rate of             PCNA in HCC was significantly higher compared to control (P<0.0001) and non-tumor             liver tissues (P<0.0001). There was a possible link between the formation of             ε-dA and chronic inflammation and fibrosis. Therefore, ε-dA lesions may gradually             accumulate in chronic liver diseases, and partially contribute to mutant p53 overexpression             and excessive cell proliferation, making it a potential mechanism in oxidative             stress-mediated hepatocarcinogenesis.
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Yang
authors.forename: Dean
authors.initials: D
authors.lastname: Tian
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D018736:DNA Adducts / Q000235:genetics / Q000378:metabolism*; D003839:Deoxyadenosines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000199:Actins; D018736:DNA Adducts; D003839:Deoxyadenosines; D018809:Proliferating Cell Nuclear Antigen; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C032221:1,N(6)-ethenodeoxyadenosine; D013482:Superoxide Dismutase