title: Activation of HSPA1A promoter by environmental pollutants: An early and rapid response to cellular damage.
abstract: We established the HepG2-luciferase cells containing a luciferase reporter gene regulated by human HSPA1A promoter. The screening of heat shock and three typical environmental toxicants revealed differences in their capacities to activate HSPA1A promoter in HepG2-luciferase cells. After heat shock, a progressive time-dependent increase in relative luciferase activity was detected peaking at 8h of recovery. Benzo[a]pyrene, formaldehyde and sodium bisulfite induced significant time-dependent elevation of relative luciferase activity, which were positively correlated with MDA concentration, Olive tail moment and micronuclei frequency. The significant increase in relative luciferase activity was already evident after 4h of benzo[a]pyrene, 1h of formaldehyde and sodium bisulfite exposure, when no increases in cellular damage were detected by other toxicity tests. Therefore, the HepG2-luciferase cells are useful model for examining the overall cellular responses to oxidative stress and genotoxic damage, and provide a reporter system for rapid and sensitive screening of environmental pollutants.
authors: School of Public Health, Medical College of Soochow University, 199 Renai Road, Suzhou 215123, Jiangsu, China. Electronic address: llxin@suda.edu.cn.
authors: Lili
authors: L
authors: Xin
authors: Suzhou Center for Disease Prevention and Control, 72 Sanxiang Road, Suzhou, Jiangsu, China.
authors: Jianshu
authors: J
authors: Wang
authors: Suzhou Industrial Park Centers for Disease Control and Prevention, 58 Suqian Road, Suzhou, Jiangsu, China.
authors: Guoqiang
authors: G
authors: Fan
authors: School of Public Health, Medical College of Soochow University, 199 Renai Road, Suzhou 215123, Jiangsu, China.
authors: Yanhu
authors: Y
authors: Wu
authors: School of Public Health, Medical College of Soochow University, 199 Renai Road, Suzhou 215123, Jiangsu, China.
authors: Sifan
authors: S
authors: Guo
mesh_terms: D001564:Benzo(a)pyrene / Q000633:toxicity; D004785:Environmental Pollutants / Q000633:toxicity*; D005557:Formaldehyde / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D056945:Hep G2 Cells; D006358:Hot Temperature; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D013447:Sulfites / Q000633:toxicity
chemical_list: D004785:Environmental Pollutants; D018840:HSP70 Heat-Shock Proteins; C490786:HSPA1A protein, human; D013447:Sulfites; D005557:Formaldehyde; D001564:Benzo(a)pyrene; D008315:Malondialdehyde; D008156:Luciferases; C009279:sodium bisulfite
keywords: Environmental pollutants; Genotoxic damage; Oxidative stress; Toxicity screening; Transcriptional activation