title: Benzo[ghi]perylene activates the AHR pathway to exert biological effects on the NL-20 human bronchial cell line.
abstract: Polycyclic aromatic hydrocarbons (PAH) are produced by incomplete combustion of organic material. In the Mexico City atmosphere, the most abundant PAH is benzo[ghi]perylene (BghiP), a gasoline combustion marker. At present, there are no reports of the effects of BghiP on human bronchial cells, so the aim of the study was to evaluate the effects in vitro of BghiP on the NL-20 cell line. Results showed that BghiP induced the formation of small vesicles throughout the cytoplasm, with absence of nuclear fragmentation. At 48h exposition, damage in cell membrane increased significantly at 1.24μg/mL of BghiP (p<0.05). Immunocytochemistry revealed that BghiP provokes nuclear translocation of AhR receptor, which indicates that this compound can induce transcription of genes via receptor binding (AhR pathway activation). BghiP induced a two-fold increase (p<0.05) in the expression of AhR and CYP4B1 (a lung-specific pathway effector). In the presence of the receptor antagonist CH-223191, the loss of viability, the nuclear translocation and the overexpression of genes decreased, though this did not prevent the formation of vesicles. BghiP induced oxidative stress and in presence of the receptor antagonist this increased significantly. In conclusion, BghiP can activate the overexpression of AhR and CYP4B1, and the effects are abated by the AhR receptor antagonist. This is the first report to prove that BghiP utilizes the AhR pathway to exert its toxic effects on the NL-20 human bronchial cell line .
authors.affiliation: Laboratorio de Investigación en Patología Experimental, Hospital Infantil de México Federico Gómez Avenida Dr. Márquez 162, Colonia Doctores, 06720 México, D.F., Mexico. Electronic address: montse_zaragoza@hotmail.com.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Zaragoza-Ojeda
authors.affiliation: Laboratorio de Biología Molecular, Departamento de Patología Clínica y Experimental, Hospital Infantil de México Federico Gómez Avenida Dr. Márquez 162, Colonia Doctores, 06720 México, D.F., Mexico. Electronic address: eguiapilar@yahoo.com.
authors.forename: Pilar
authors.initials: P
authors.lastname: Eguía-Aguilar
authors.affiliation: Laboratorio de Biología Molecular, Departamento de Patología Clínica y Experimental, Hospital Infantil de México Federico Gómez Avenida Dr. Márquez 162, Colonia Doctores, 06720 México, D.F., Mexico. Electronic address: mpdiazconti@gmail.com.
authors.forename: Mario
authors.initials: M
authors.lastname: Perezpeña-Díazconti
authors.affiliation: Laboratorio de Investigación en Patología Experimental, Hospital Infantil de México Federico Gómez Avenida Dr. Márquez 162, Colonia Doctores, 06720 México, D.F., Mexico. Electronic address: farenashuertero@yahoo.com.mx.
authors.forename: Francisco
authors.initials: F
authors.lastname: Arenas-Huertero
mesh_terms: D021581:Active Transport, Cell Nucleus; D000393:Air Pollutants / Q000633:toxicity*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D019570:Inhalation Exposure; D018384:Oxidative Stress / Q000187:drug effects; D010569:Perylene / Q000031:analogs & derivatives* / Q000633:toxicity; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D001189:Aryl Hydrocarbon Hydroxylases; D051792:Basic Helix-Loop-Helix Proteins; D010569:Perylene; D018336:Receptors, Aryl Hydrocarbon; D001335:Vehicle Emissions; C111235:AHR protein, human; C006718:1,12-benzoperylene; C095029:cytochrome P-450 CYP4B1
keywords: AhR; Air pollution; Benzo(ghi)perylene; Oxidative stress; Polycyclic aromatic hydrocarbons