Radon-induced alterations in p53-mediated energy metabolism of malignantly transformed human bronchial epithelial cells.
Radon and its progeny were confirmed to be a category I carcinogenic agent. However, the molecular basis underlying carcinogenesis induced by radon has not been fully elucidated. Expression of p53, a key regulator in glycolysis, is known to be decreased in carcinogenesis. The aim of this investigation was to determine changes in energy metabolism mediated by p53-related metabolic pathway using radon-induced transformation of human bronchial epithelial (HBE) cells. HBE cells were exposed to radon for 20 min at a concentration of 20,000 Bq/m(3) and cultured for 3 d, and exposed again at the same concentration and duration. This was repeated 10 times with culture for 35 passages until malignant transformation occurred. During the culturing process, the levels of lactate and lactate dehydrogenase (LDH) and ratio of NAD(+)/NADH gradually increased between passages. Between passages 30 and 35, p53 target gene synthesis of cytochrome c oxidase 2 (SCO2), TP53-induced glycolysis, and apoptosis regulator (TIGAR) expression were significantly decreased. Data demonstrated that p53-associated metabolic pathways may be altered in radon-mediated malignant transformation.
a Department of Toxicology , School of Public Health, Medical College of Soochow University , No.199 Ren-Ai Road, Suzhou , China.
Xing
X
Liu
a Department of Toxicology , School of Public Health, Medical College of Soochow University , No.199 Ren-Ai Road, Suzhou , China.
Xu
X
Wang
a Department of Toxicology , School of Public Health, Medical College of Soochow University , No.199 Ren-Ai Road, Suzhou , China.
Jian
J
Tong
D001980:Bronchi / Q000187:drug effects; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016158:Genes, p53 / Q000187:drug effects*; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology; D011886:Radon / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects*
D011886:Radon