基于周期阻滞和氧化-抗氧化失衡研究槟榔碱致小鼠骨髓细胞DNA损伤的机制OA

Objective:To study the DNA damage effect of arecoline(ARC)on mouse bone marrow cells in vivo,and to ex-plore its mechanism.Methods:Single cell gel electrophoresis was used to analyze the DNA damage effect of ARC on mouse bone marrow cells.Flow cytometry,DCFH-DA fluorescence staining,and Rhodamine 123 staining were used to analyze the cell cycle,superoxide dismutase(SOD)activity,glutathione(GSH),malondial dehyde(MDA),and reactive oxygen species(ROS)content,mitochondrial transmembrane potential(Δψm)and p53 protein content of mouse bone marrow cells.Results:ARC,at a dose of 1/2 LD50,could induce DNA damage in mouse bone marrow cells.The difference was significant compared to the negative control group.Cell cycle changed observably in a dose-dependent manner when exposed to ARC.The percentage of cells in G0/G1 phase was significantly increased(P<0.01),and ARC caused G0/G1 phases' cell cycle arrest in mouse bone marrow cells.After the ad-ministration of ARC,SOD activity and GSH content were significantly decreased(P<0.01),MDA and ROS contents were sig-nificantly increased(P<0.01).Furthermore,the Δψm was significantly reduced with increasing dose(P<0.01).The protein lev-els of p53 in mouse bone marrow cells was increased in a dose-dependent manner after ARC treatment(P<0.01).Conclusion:ARC can cause DNA damage of mouse bone marrow cells,increase the expression of p53 protein causing cell cycle arrest in the G0/G1 phase,decrease Δψm,increase ROS in mouse bone marrow cells,enhance lipid peroxidation,severely damage cellular an-tioxidant function,and lead to the imbalance of oxidation and antioxidation.These are the mechanisms of DNA damage in mouse bone marrow cells caused by ARC.