Exploring Of Down-regulated Expression Of HOGG1 Gene In Pathogenesis And Therapeutic Mechanism Of Lung Cancer

With the progress of technology and the development of industry and argriculture, more and more carcinogens and pollutants had come into environment. Asenic, PAHs, asbestus, coal tar and tobacoo smoke, vehicle emissions, cooking oil fumes and so on were all regarded to be important reasons for lung cancer. Toxicologic and molecular epidemiologic studies suggested that enviromental carcinogens and pollutants could change the level of 8-oxoguanine(8-OHdG) by oxidative DNA damage. Human 8-oxoguanine DNA glycosylase-1(hOGG1) was a crucial enzyme which could excise and repair 8-OHdG. To investigate the effect of down-regulated expression of hOGG1 gene in sensitivity of lung adenocarcinoma cells to oxidative damage, and provide more evidence to the viewpoint that environmental carcinogens and pollutants induced lung cancer by oxidative damage, we vallidated the stable transfection of hammerhead ribozyme gene targeting to hOGG1 mRNA by tolerance of hygromycin (G418) firstly, and identified the biological characteristics of A549-R cells with down-regulated expressed hOGG1 gene by observing the cell morphology, growth curve, proliferation doubling-time and the clone formation ability, then compared the oxidative DNA damage and repair of A549 cells and A549-R cells exposed to sodium dichromate, benzo(a)pyrene, extract of vehicle emissions, extract of tobacco smoke and cooking oil fumes condensate by MTT method, comet assay and detection of antioxidative enzyme activety. The results showed that A549-R cells had resistance to G418, while A549 cells failed to...