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Progress in Assessing Air Pollutant Risks from In Vitro Exposures: Matching Ozone Dose and Effect in Human Air Way Cells
Citation:
Hatch, G., K. Duncan, D. Diaz-Sanchez, Mike Schmitt, Andy Ghio, Martha Sue Carraway, J. Mckee, L. Dailey, J. Berntsen, AND R. Devlin. Progress in Assessing Air Pollutant Risks from In Vitro Exposures: Matching Ozone Dose and Effect in Human Air Way Cells. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 141(1):198-205, (2014).
Impact/Purpose:
The paper makes an important step toward the NexGen goal of using in vitro data for risk assessments. It establishes the connection between in vitro and in vivo dose of the prototypic air pollutant, ozone.
Description:
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 03 in airway cells of humans exposed in vivo to that of human cells exposed in vitro. Ten subjects breathed labeled 03 ((18)03, 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) 03 for 2 h. The 03 dose to the cells was defined as the level of (18)0 incorporation and the 03 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)03 concentration in vitro suggesting upper airway 03 scrubbing in vivo. Cells collected by lavage as well as previous studies in monkeys show that cells deeper in the lung receive a higher 03 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 03 in an in vitro system.