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DOI10.1093/toxsci/kfu115
Progress in Assessing Air Pollutant Risks from In Vitro Exposures: Matching Ozone Dose and Effect in Human Airway Cells
Hatch, Gary E.1; Duncan, Kelly E.2; Diaz-Sanchez, David1; Schmitt, Michael T.1; Ghio, Andrew J.1; Carraway, Martha Sue1; McKee, John1; Dailey, Lisa A.1; Berntsen, Jon3; Devlin, Robert B.1
发表日期2014-09-01
ISSN1096-6080
卷号141期号:1页码:198-205
英文摘要

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 O-3 in airway cells of humans exposed in vivo to that of human cells exposed in vitro. Ten subjects breathed labeled O-3 (O-18(3), 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 O-18(3) for 2 h. The O-3 dose to the cells was defined as the level of O-18 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 vivo exposed subjects were lower than in cells exposed to the same O-18(3) concentration in vitro suggesting upper airway O-3 scrubbing in vivo. 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 vivo dose and effect of O-3 in an in vitro system.


英文关键词ozone;in vivo versus in vitro dose;extrapolation;epithelial cells;bronchoalveolar lavage
语种英语
WOS记录号WOS:000342990200024
来源期刊TOXICOLOGICAL SCIENCES
来源机构美国环保署
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/59395
作者单位1.US EPA, Environm Publ Hlth Div, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA;
2.Univ N Carolina, Sch Med, Ctr Environm Med Asthma & Lung Biol, Chapel Hill, NC 27599 USA;
3.TRC Environm Corp, Raleigh, NC 27606 USA
推荐引用方式
GB/T 7714
Hatch, Gary E.,Duncan, Kelly E.,Diaz-Sanchez, David,et al. Progress in Assessing Air Pollutant Risks from In Vitro Exposures: Matching Ozone Dose and Effect in Human Airway Cells[J]. 美国环保署,2014,141(1):198-205.
APA Hatch, Gary E..,Duncan, Kelly E..,Diaz-Sanchez, David.,Schmitt, Michael T..,Ghio, Andrew J..,...&Devlin, Robert B..(2014).Progress in Assessing Air Pollutant Risks from In Vitro Exposures: Matching Ozone Dose and Effect in Human Airway Cells.TOXICOLOGICAL SCIENCES,141(1),198-205.
MLA Hatch, Gary E.,et al."Progress in Assessing Air Pollutant Risks from In Vitro Exposures: Matching Ozone Dose and Effect in Human Airway Cells".TOXICOLOGICAL SCIENCES 141.1(2014):198-205.
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