Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China.
Oncol Rep. 2013 Mar;29(3):875-84. doi: 10.3892/or.2013.2227. Epub 2013 Jan 4.
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.
大量研究发现，氧化应激衍生的 1，N6-烯丙基脱氧腺苷（ε-dA）可作为癌症易患肝脏疾病中肝细胞癌（HCC）的驱动力。本研究旨在确定 HCC 及相邻非肿瘤肝组织中的氧化应激状态和 ε-dA 的发生情况，并阐明 ε-dA 的发生是否与肝炎症活动、纤维化和突变型 p53 表达有关。检查了 32 例 HCC 患者肿瘤和（或）非肿瘤肝组织中的氧化应激相关参数。在对照、HCC 和非肿瘤肝组织中进行了 ε-dA、突变型 p53 和增殖细胞核抗原（PCNA）的免疫组织化学研究。与非肿瘤组织相比，HCC 组织的总抗氧化能力和总超氧化物歧化酶活性均较低（P<0.05 比 P<0.001）。与对照（P<0.0001）和非肿瘤肝组织（P<0.001）相比，HCC 中 ε-dA 的发生率显著更高。观察到 ε-dA 阳性率与突变型 p53 之间存在显著相关性（r=0.5162，P<0.01）。HCC 中 PCNA 的阳性率明显高于对照（P<0.0001）和非肿瘤肝组织（P<0.0001）。ε-dA 损伤的形成与慢性炎症和纤维化之间可能存在联系。因此，ε-dA 损伤可能在慢性肝病中逐渐积累，并部分导致突变型 p53 过表达和过度细胞增殖，成为氧化应激介导的肝癌发生的潜在机制。
