Radon-induced reduced apoptosis in human bronchial epithelial cells with knockdown of mitochondria DNA.
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.
Department of Toxicology, School of Public Health, Soochow University, Suzhou, China.
Bing-Yan
BY
Li
Jing
J
Sun
Hong
H
Wei
Yu-Zhi
YZ
Cheng
Lian
L
Xue
Zhi-Hai
ZH
Cheng
Jian-Mei
JM
Wan
Ai-Qing
AQ
Wang
Tom K
TK
Hei
Jian
J
Tong
D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D002274:Carcinogens, Environmental / Q000633:toxicity*; D002453:Cell Cycle / Q000528:radiation effects; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects; D004272:DNA, Mitochondrial / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004996:Ethidium / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D006801:Humans; D007364:Intercalating Agents / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000528:radiation effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D011886:Radon / Q000633:toxicity*; D017687:Radon Daughters / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D036401:Toxicity Tests, Chronic / Q000379:methods
D002274:Carcinogens, Environmental; D004272:DNA, Mitochondrial; D007364:Intercalating Agents; D017687:Radon Daughters; D017382:Reactive Oxygen Species; D004996:Ethidium; D011886:Radon