title: Progress in assessing air pollutant risks from in vitro exposures: matching ozone dose and effect in human airway cells.
abstract: In vitro exposures to air pollutants could, in theory, facilitate a rapid and detailed assessment of molecular mechanisms of toxicity. However, it is difficult to ensure that the dose of a gaseous pollutant to cells in tissue culture is similar to that of the same cells during in vivo exposure of a living person. The goal of the present study was to compare the dose and effect of O3 in airway cells of humans exposed in vivo to that of human cells exposed in vitro. Ten subjects breathed labeled O3 ((18)O3, 0.3 ppm, 2 h) while exercising intermittently. Bronchial brush biopsies and lung lavage fluids were collected 1 h post exposure for in vivo data whereas in vitro data were obtained from primary cultures of human bronchial epithelial cells exposed to 0.25-1.0 ppm (18)O3 for 2 h. The O3 dose to the cells was defined as the level of (18)O incorporation and the O3 effect as the fold increase in expression of inflammatory marker genes (IL-8 and COX-2). Dose and effect in cells removed from in vivo exposed subjects were lower than in cells exposed to the same (18)O3 concentration in vitro suggesting upper airway O3 scrubbing in vivo. Cells collected by lavage as well as previous studies in monkeys show that cells deeper in the lung receive a higher O3 dose than cells in the bronchus. We conclude that the methods used herein show promise for replicating and comparing the in vivo dose and effect of O3 in an in vitro system.
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711 hatch.gary@epa.gov.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Hatch
authors.affiliation: Center for Environmental Medicine, Asthma and Lung Biology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599.
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Duncan
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
authors.forename: David
authors.initials: D
authors.lastname: Diaz-Sanchez
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Schmitt
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ghio
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
authors.forename: Martha Sue
authors.initials: MS
authors.lastname: Carraway
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
authors.forename: John
authors.initials: J
authors.lastname: McKee
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Dailey
authors.affiliation: TRC Environmental Corporation, Raleigh, North Carolina 27606.
authors.forename: Jon
authors.initials: J
authors.lastname: Berntsen
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Devlin
mesh_terms: D000328:Adult; D000393:Air Pollutants / Q000633:toxicity*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D001999:Bronchoscopy; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics; D008297:Male; D010103:Oxygen Isotopes; D010126:Ozone / Q000633:toxicity*; D018570:Risk Assessment; D055815:Young Adult
chemical_list: D000393:Air Pollutants; D016209:Interleukin-8; D010103:Oxygen Isotopes; D010126:Ozone; D051546:Cyclooxygenase 2
keywords: bronchoalveolar lavage; epithelial cells; extrapolation; in vivo versus in vitro dose; ozone