Mechanism Of Lung Cancer Induced Jointly By Radon And Smoking

Objective and meaning: in this study, we established a cultured cell model in vitro to investigate associate effects of Alpha-irradiation and CSC on cytotoxicity and genotoxicity. it provided experimental and theoretic evidences to evaluate the carcinogenesis risk of randon and smoking.Material and Methods: Immortalized human bronchial epithelial cells (BEP2D) were divided into five groups, namely normal control (NC), alpha-particles irradiation (a), CSC administration (CSC), alpha-particles irradiation before CSC administration (a+CSC) and after administration CSC (CSC+a), for investigating some data about the cell toxicity and malignant transformation effect.Results: (1) We obtained the result of cell survival curve that the LC50 of BEP2D cells dealing with CSC alone or irradiated withα-particle was 3μg/ml and 0.7Gy separately. (2) These data including the content of ROS, LDH, NAO, MDA, SOD, SeGPx, and the apoptosis rate, the DNA damage indexes and the product of 8-dG revealed a significant effect on the BEP2D cells by poisoning with CSC or irradiating withα-particle. And the result showed an obvious relation between dose and effect. Especially the combination role of CSC andα-particle injured the BEP2D cells more seriously. (3) In a lower dose of CSC, these data such as NAO, MDA, SOD, SeGPx and the apoptosis rate by poisoning with CSC first and then irradiating withα-particle were lower than the expected value by the combination role of CSC andα-particle. And the role by poisoning with CSC first and then irradiating withα-particle showed positive cooperatives. The change in the ordinal difference of the combination role didn't be found in the other data. (4) The BEP2D cells by irradiating withα-particle first and then poisoning with CSC 24h were cultured continuously to the pass 35. We obtained the earlier transformed cell and analyzed its biological characteristics. Results showed that the BEP2D cells had lost the contact inhibition; their survival ability in vitro increased obviously and obtained the anchoring growth ability independently. The cell cycle disordered that the rate of G0/G1 cells decreased, the rate of G2/M cells increased and the S- cells shortened significantly. The spontaneous apoptosis were increased. So, we thought that the BEP2D cells by treating with CSC andα-particle had transformed into malignant cells.Conclusion: it was demonstrated there were significant associate effects of alpha particles and CSC on cytotoxicity and genotoxicity, and certain indicators showed difference due to administration order. Alpha-particles irradiation before CSC administration (α+CSC) has higher risk of carcinogenesis than alpha-particles irradiation after CSC administration (CSC+α).