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Objective: To study the mechanism on malignant transformation of human bronchial epithelial cell line BEP2D induced by α-particles exposure.Methods: Using DCFH-DA, the intracellular generation of ROS was monitored by fluorescence microscope in BEP2D, RH22 (passage 22 of α-particles-irradiated BEP2D cells) and BERP35T-1 cells (derived from nude mice bearing malignant transformed cells generated from cells of passage 35 of α-particles-irradiated BEP2D cells).Malonaldehyde (MDA) contents assay was applied for the detection of the levels of MDA in BEP2D, RH22 and BERP35T-1 cells.Immunocytochemistry and immunofluorescence staining were used to compare the differences of the expression levels of 8-OH-dG and γH2AX in BEP2D, RH23 (passage 23 of α-particles-irradiated BEP2D cells) and BERP35T-1 cells.Results: Compared to BEP2D cells, the levels of ROS (t=4.30 and 3.94, P<0.05) and MDA (t=4.89 and 15.10, P<0.05) increased in RH22 and BERP35T-1 cells.The expression levels of 8-OH-dG (t=3.80 and 2.92, P<0.05) and γH2AX (t=7.61 and 12.67,P<0.05) in RH23 and BERP35T-1 cells were higher than those in BEP2D cells.Conclusions:Oxidative stress induces lipid peroxidation and DNA damage leading to increased genomic instability, which could contribute to the acceleration of cellular malignant transforming process in the malignant transformed human bronchial epithelial cell line BEP2D induced by α-particles exposure.