Oxidative stress induces B lymphocyte DNA damage and apoptosis by upregulating p66shc

J.-Y. Lang, K. Ma, J.-X. Guo, H. Sun

Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. huisunr@126.com

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• Hematology

OBJECTIVE: B lymphoma is a type of malignant tumor originating from the lymphatic hematopoietic system. The pathogenesis and treatment methods are not clear. The change of oxidative stress is closely related to the cell DNA damage and cell apoptosis, which may be served as a target for cancer treatment. This study aims to illustrate the role of oxidative stress in the regulation of B lymphocytoma.

PATIENTS AND METHODS: The tumor tissue was collected from patients with B lymphocytoma. The p66shc level was detected by Western blot. Hydrogen peroxide (H₂O₂) was assessed by the kit. The oxidative stress model of B lymphoma cell was established by H₂O₂ treatment. ROS inhibitor or RNAi was used to regulate ROS level. ROS level was determined by flow cytometry. 8-OHdG level (DNA damage product) was tested by the kit. Cell apoptosis was evaluated by annexin V-PI.

RESULTS: P66shc expression was significantly reduced, while H₂O₂ production was significantly decreased in the tumor tissue of B lymphoma compared with adjacent normal control. H₂O₂ stimulation markedly elevated ROS level and p66shc expression (p < 0.05), accompanied by the aggravation of DNA damage and increase of apoptosis. ROS inhibitor or p66shc RNAi treatment significantly attenuated DNA damage and declined cell apoptosis (p < 0.05).

CONCLUSIONS: ROS production promoted p66shc expression, induced DNA damage, and facilitated cell apoptosis. Upregulation of p66shc by oxidative stress could be treated as a new therapeutic target for B lymphoma.

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