Progress in assessing air pollutant risks from in vitro exposures: matching ozone dose and effect in human airway cells.
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.
['Hatch|Gary E|GE|', 'Duncan|Kelly E|KE|', 'Diaz-Sanchez|David|D|', 'Schmitt|Michael T|MT|', 'Ghio|Andrew J|AJ|', 'Carraway|Martha Sue|MS|', 'McKee|John|J|', 'Dailey|Lisa A|LA|', 'Berntsen|Jon|J|', 'Devlin|Robert B|RB|']
D000328:Adult D000393:Air Pollutants D001980:Bronchi D001992:Bronchoalveolar Lavage Fluid D001999:Bronchoscopy D002478:Cells, Cultured D051546:Cyclooxygenase 2 D004305:Dose-Response Relationship, Drug D004847:Epithelial Cells D005260:Female D015870:Gene Expression D006801:Humans D016209:Interleukin-8 D008297:Male D010103:Oxygen Isotopes D010126:Ozone D018570:Risk Assessment D055815:Young Adult
ozone epithelial cells bronchoalveolar lavage extrapolation in vivo versus in vitro dose