title: Exposure Cessation During Adulthood Did Not Prevent Immunotoxicity Caused by Developmental Exposure to Low-Level Trichloroethylene in Drinking Water.
abstract: Exposure to the water pollutant trichloroethylene (TCE) can promote autoimmunity in both humans and rodents. Using a mouse model we have shown that chronic adult exposure to TCE at 500 μg/ml in drinking water generates autoimmune hepatitis in female MRL+/+ mice. There is increasing evidence that developmental exposure to certain chemicals can be more toxic than adult exposure. This study was designed to test whether exposure to a much lower level of TCE (0.05 μg/ml) during gestation, lactation, and early life generated autoimmunity similar to that found following adult exposure to higher concentrations of TCE. When female MRL+/+ mice were examined at postnatal day (PND) 259 we found that developmental/early life exposure [gestational day 0 to PND 154] to TCE at a concentration 10 000 fold lower than that shown to be effective for adult exposure triggered autoimmune hepatitis. This effect was observed despite exposure cessation at PND 154. In concordance with the liver pathology, female MRL+/+ exposed during development and early life to TCE (0.05 or 500 μg/ml) generated a range of antiliver antibodies detected by Western blotting. Expression of proinflammatory cytokines by CD4+ T cells was also similarly observed at PND 259 in the TCE-exposed mice regardless of concentration. Thus, exposure to TCE at approximately environmental levels from gestational day 0 to PND 154 generated tissue pathology and CD4+ T cell alterations that required higher concentrations if exposure was limited to adulthood. TCE exposure cessation at PND 154 did not prevent the immunotoxicity.
authors.affiliation: Department of Microbiology and Immunology, Department of Biochemistry and Molecular Biology, Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Research Institute, Little Rock, Arkansas, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Gilbert
authors.affiliation: Department of Microbiology and Immunology, Department of Biochemistry and Molecular Biology, Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Research Institute, Little Rock, Arkansas, USA.
authors.forename: Shasha
authors.initials: S
authors.lastname: Bai
authors.affiliation: Department of Microbiology and Immunology, Department of Biochemistry and Molecular Biology, Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Research Institute, Little Rock, Arkansas, USA.
authors.forename: Dustyn
authors.initials: D
authors.lastname: Barnette
authors.affiliation: Department of Microbiology and Immunology, Department of Biochemistry and Molecular Biology, Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Research Institute, Little Rock, Arkansas, USA.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Blossom
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005260:Female; D019693:Hepatitis, Autoimmune / Q000209:etiology* / Q000276:immunology; D019463:Mice, Inbred MRL lpr; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000276:immunology; D014241:Trichloroethylene / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D014874:Water Pollutants, Chemical; D014241:Trichloroethylene
keywords: autoimmune; developmental exposure and adult disease; trichloroethylene