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Abstract
Radon and radon progeny inhalation exposure are recognized to induce lung cancer. To explore the role of mitochondria in radon-induced carcinogenesis in humans, an in vitro partially depleted mitochondrial DNA (mtDNA) cell line (ρ–) was generated by treatment of human bronchial epithelial (HBE) cells (ρ+) with ethidium bromide (EB). The characterization of ρ– cells indicated the presence of dysfunctional mitochondria and might thus serve a reliable model to investigate the role of mitochondria. In a gas inhalation chamber, ρ– and ρ+ cells were exposed to radon gas produced by a radium source. Results showed that apoptosis was significantly increased both in ρ– and ρ+ cells irradiated by radon. Moreover, apoptosis in ρ– cells showed a lower level than in ρ+ cells. Radon was further found to depress mitochondrial membrane potential (MMP) of HBE cells with knockdown mtDNA. Production of reactive oxygen species (ROS) was markedly elevated both in ρ– and ρ+ cells exposed to radon. The distribution of phases of cell cycle was different in ρ– compared to ρ+ cells. Radon irradiation induced a rise in G2/M and decrease in S phase in ρ+ cells. In ρ– cells, G1, G2/M, and S populations remained similar to cells exposed to radon. In conclusion, radon–induced changes in ROS generation, MMP and cell cycle are all attributed to reduction of apoptosis, which may trigger and promote cell transformation, leading to carcinogenesis. Our study indicates that the use of the ρ– knockdown mtDNA HBE cells may serve as a reliable model to study the role played by mitochondria in carcinogenic diseases.
Acknowledgments
The work was supported by the National Natural Science Foundation grants 81020108028 and 81072286, and in part by funding from the National Institutes of Health grants ES05786 and CA49062, Superfund grant P42 ES10349, and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).
Notes
Bing-Yan Li and Jing Sun contributed equally to this work.