Progress in Assessing Air Pollutant Risks from In Vitro Exposures: Matching Ozone Dose and Effect in Human Airway Cells

摘要

In uitro 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 O_3 in airway cells of humans exposed in uiuo to that of human cells exposed in uitro. Ten subjects breathed labeled O3 (~(18)O_3, 0.3 ppm, 2 h) while exercising intermittently. Bronchial brush biopsies and lung lavage fluids were collected 1 h post exposure for in uiuo data whereas in uitro data were obtained from primary cultures of human bronchial epithelial cells exposed to 0.25-1.0 ppm ~(18)O_3 for 2 h. The O_3 dose to the cells was defined as the level of ~(18)O incorporation and the O_3 effect as the fold increase in expression of inflammatory marker genes (IL-8 and COX-2). Dose and effect in cells removed from in uiuo exposed subjects were lower than in cells exposed to the same ~(18)O_3 concentration in vitro suggesting upper airway O_3 scrubbing in uiuo. Cells collected by lavage as well as previous studies in monkeys show that cells deeper in the lung receive a higher O_3 dose than cells in the bronchus. We conclude that the methods used herein show promise for replicating and comparing the in uiuo dose and effect of O_3 in an in vitro system.