title: The effect of in vitro dieldrin exposure on the rat paraoxonase 1 (pon1) promoter.
abstract: The legacy organochlorine insecticide, dieldrin, is still found in soil and accumulation in individuals is possible. Paraoxonase 1 hydrolyzes the oxon metabolites of organophosphorus insecticides, as well as other substrates. Putative binding sites for pregnane X receptor (PXR) exist in the paraoxonase promoter, and studies have indicated that dieldrin can activate PXR-regulated gene expression. We examined rat paraoxonase promoter activity in the presence of dieldrin alone or combined with nuclear receptors (NRs). In vitro dieldrin concentrations from 10 to 100 µM significantly increased (p < 0.05) promoter activity in the presence of Pxr or Rxrα alone and when Pxr plus Rxrα were on the same vector, indicating that dieldrin can increase paraoxonase promoter activity in the presence of NRs. To our knowledge, this is the first report of dieldrin increasing paraoxonase promoter activity. Since many organochlorine insecticides are in the same chemical class as dieldrin, these results could be typical of other bioaccumulative persistent pollutants.
authors.affiliation: Center for Environmental Health Sciences and Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, USA.
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Dail
authors.forename: Rebecca
authors.initials: R
authors.lastname: Pickin
authors.forename: John Allen
authors.initials: JA
authors.lastname: Crow
authors.forename: Janice E
authors.initials: JE
authors.lastname: Chambers
mesh_terms: D000818:Animals; D043303:Aryldialkylphosphatase / Q000737:chemistry / Q000235:genetics; D001665:Binding Sites; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D004026:Dieldrin / Q000737:chemistry / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects*; D008163:Luminescent Measurements; D057093:Orphan Nuclear Receptors / Q000737:chemistry / Q000378:metabolism; D010957:Plasmids; D000077297:Pregnane X Receptor; D011401:Promoter Regions, Genetic; D051381:Rats; D011987:Receptors, Steroid / Q000737:chemistry / Q000378:metabolism*; D012989:Soil Pollutants / Q000737:chemistry / Q000633:toxicity*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D014162:Transfection
chemical_list: D057093:Orphan Nuclear Receptors; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D012989:Soil Pollutants; C016658:phorbolol myristate acetate; C572204:Pon1 protein, rat; D043303:Aryldialkylphosphatase; D004026:Dieldrin; D013755:Tetradecanoylphorbol Acetate
keywords: Dieldrin; PXR; Paraoxonase 1 (PON1); RXRα