Oxidative stress-induced 1, N6-ethenodeoxyadenosine adduct formation contributes to hepatocarcinogenesis

Numerous studies have found that oxidative stress-derived 1, N-6-ethenodeoxyadenosine (epsilon-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 epsilon-dA in HCC and adjacent non-tumor liver tissue, and to clarify whether the occurrence of epsilon-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. epsilon-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 epsilon-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 epsilon-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 epsilon-dA and chronic inflammation and fibrosis. Therefore, epsilon-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.