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A Simplified and Rapid Screening Assay using Zebrafish to Assess Cardiac Effects of Air Pollution-derived Particulate Matter
Stevens, J., S. Padilla, A. Tennant, R. Conolly, D. DeMarini, I. Gilmour, N. Coates, Bill Linak, D. Winsett, W. Cascio, M. Hazari, AND A. Farraj. A Simplified and Rapid Screening Assay using Zebrafish to Assess Cardiac Effects of Air Pollution-derived Particulate Matter. Society of Toxicology, San Diego, CA, March 22 - 26, 2015.
Comparative toxicity assessment of particulate matter (PM) from different sources will potentially inform the understanding of regional differences in PM-induced cardiac health effects by identifying PM sources linked to highest potency components. Conventional low-throughput in vivo methods are impractical for the cardiotoxicity assessment of countless unique PM mixtures. The purpose of this study was to develop a vertebrate model (zebrafish; Danio rerio) that will enable rapid screening of hundreds to thousands of PMs. Heart rate (HR) responses to drugs in zebrafish predict cardiac membrane activity in man. Moreover, zebrafish embryo skin is permeable to small molecules and is the primary route of oxygenation, analogous to human alveolar epithelium, the key target tissue of fine PM. Here, we present a rapid screening assay that builds on previous models and relies on a simplified health effect metric, i.e. HR, obtained using basic light microscopy and automated video imaging. High resolution videos of all wells on a 96-well plate were obtained in 50 minutes enabling derivation of HR from all fish within each well (up to 5 per well) using analysis software and a command line interface. Responses were measured in dechorionated, unanesthetized, and unrestrained 2 day old zebrafish embryos. Clonidine, an anti-hypertensive drug used as a positive control, caused concentration-dependent decreases in HR. An organic extract derived from diesel exhaust PM also caused concentration-dependent decreases in HR. This approach may expedite comparative toxicity assessments of PM sources and help identify PM components that impact cardiac electrical and mechanical properties (This abstract does not reflect USEPA policy).
This approach may enable rapid screening of hundreds to thousands of PMs, not possible with other in vivo models, accelerating the pace at which toxicity information is acquired/processed. This may significantly expedite comparative toxicity assessments and risk determinations of PM, and facilitate identification of the most toxic sources, causal components and their mode of action.
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
ENVIRONMENTAL PUBLIC HEALTH DIVISION
CARDIOPULMONARY AND IMMUNOTOXICOLOGY BRANCH