Associate Effects Of Alpha-irradiation And NNK On BEP2D Cells

Background and Objective: Smoking and environmental radon are two major factors for causing lung cancer. Studies on lung cancer induced by smoking or radon were extensively performed, however, few reports focused on interaction of smoking and radon. In this study, it was investigated that associate effects of alpha-particle irradiation and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on cultured cells in vitro in order to provide experimental evidences for combined risk assessment of smoking and environmental radon.Material and Methods: Immortalized human bronchial epithelial cells (BEP2D) were divided into five groups, namely normal control (NC), alpha particles irradiation (α), NNK administration (NNK), alpha-particle irradiation before NNK administration (100μg/ml) (α+NNK) and after administration NNK (NNK+α), for investigating the cytotoxicity, genotoxicity, oncogenic transformation and relative mechanism of alpha-particle irradiation associated NNK treatment.Results: (1) Associate effect of alpha particles and NNK on cell survival was found, in which there was difference with administration order. (2) There were obvious synergisticity of alpha particles and NNK administration on the levels of intracellular ROS, lesion of membrane permeability, DNA damage, HPRT gene mutation and micronucleus formation. (3) During the process of cell transformation, measurement results of morphology characters, growth kinetics, resistance to serum-induced differentiation and anchorage-independence growth showed malignant transformation in cells of NNK, NNK+α, α+NNK groups, and changes of chromosomes, increase of HPRT gene mutation frequencies and expression levels of PCNA and P53 were detected.Conclusion: It was demonstrated there were associate effects of alpha particle and NNK on cytotoxicity and genotoxicity, and certain indicators showed difference due to administration order.