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Activation of human peroxisome-activated receptor-gamma (PPARy) by house dust extracts
Wolf, Cynthiaj, M. Fang, H. Stapleton, AND B. Abbott. Activation of human peroxisome-activated receptor-gamma (PPARy) by house dust extracts. Presented at Teratology Society Annual Meeting, Bellevue, WA, June 28 - July 02, 2014.
This abstract will be presented at the Teratology Society Annual Meeting, June 28-July 2, 2014, Bellevue, WA, USA
Obesity in children has become an epidemic and recent research suggests a possible contribution from exposure to environmental chemicals. Several chemicals, such as phthalates, brominated flame retardants, and perfluorinated chemicals, are common in house dust on floors where children play and are suspected obesogens. Obesogens can act via a mechanism that involves activation of peroxisome proliferator-activated receptor-gamma (PPARy). A previous study found that dust collected from children’s homes binds to PPARy. Here, we investigated the ability of house dust to activate PPARy in a transiently transfected cell assay. Dust samples were collected in 2012 from carpeted and hardwood floors in children’s homes using thimbles fitted into a vacuum cleaner hose (“TEO” samples), or from homes in an adult cohort NIEHS study. Dust was extracted with 50:50 hexane:acetone, sonicated, centrifuged, and the organic layer collected. This was repeated 2X. The extracts were filtered to remove particulates, dried with purified nitrogen, and reconstituted in DMS0 at 200 ug/ul. COS-1 cells were transfected for 24 hrs with a human PPARy vector containing a luciferase reporter, and exposed for 24 hrs to negative controls water or DMSO (0.1%), positive controls Troglitazone (3 uM in water) or Rosiglitazone (100 nM in DMSO), or dust extracts serially diluted in DMEM at 50, 100, and 200 ug/ml in 0.1% DMSO. Cells were lysed and luciferase activity was measured. Data were log-transformed and normalized to DMSO or water controls (as appropriate). All TEO samples activated PPARy at 200 ug/ml, some TEO were active at 50 or 100 ug/ml, and there was a significant concentration-response trend with some samples. Generally, the NIEHS samples were less active, but some activated PPARy at 200 ug/ml and showed a concentration-response trend. This study found that chemicals in house dust can activate human PPARy in a transfected cell culture system. This abstract does not necessarily reflect USEPA policy.
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
TOXICOLOGY ASSESSMENT DIVISION
DEVELOPMENTAL TOXICOLOGY BRANCH