title: Low-dose trichloroethylene alters cytochrome P450-2C subfamily expression in the developing chick heart.
abstract: Trichloroethylene (TCE) is an organic solvent and common environmental contaminant. TCE exposure is associated with heart defects in humans and animal models. Primary metabolism of TCE in adult rodent models is by specific hepatic cytochrome P450 enzymes (Lash et al. in Environ Health Perspect 108:177-200, 2000). As association of TCE exposure with cardiac defects is in exposed embryos prior to normal liver development, we investigated metabolism of TCE in the early embryo. Developing chick embryos were dosed in ovo with environmentally relevant doses of TCE (8 and 800 ppb) and RNA was extracted from cardiac and extra-cardiac tissue (whole embryo without heart). Real-time PCR showed upregulation of CYP2H1 transcripts in response to TCE exposure in the heart. No detectable cytochrome expression was found in extra-cardiac tissue. As seen previously, the dose response was non-monotonic and 8 ppb elicited stronger upregulation than 800 ppb. Immunostaining for CYP2C subfamily expression confirmed protein expression and showed localization in both myocardium and endothelium. TCE exposure increased protein expression in both tissues. These data demonstrate that the earliest embryonic expression of phase I detoxification enzymes is in the developing heart. Expression of these CYPs is likely to be relevant to the susceptibility of the developing heart to environmental teratogens.
authors.affiliation: Department of Cell Biology and Anatomy, University of Arizona, 1501 N Campbell Avenue, LSN 456, PO Box 245044, Tucson, AZ 85724-5044, USA.
authors.forename: Om
authors.initials: O
authors.lastname: Makwana
authors.forename: Lauren
authors.initials: L
authors.lastname: Ahles
authors.forename: Alejandro
authors.initials: A
authors.lastname: Lencinas
authors.forename: Ornella I
authors.initials: OI
authors.lastname: Selmin
authors.forename: Raymond B
authors.initials: RB
authors.lastname: Runyan
mesh_terms: D000818:Animals; D002642:Chick Embryo; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000196:embryology*; D012997:Solvents / Q000008:administration & dosage; D014241:Trichloroethylene / Q000008:administration & dosage*
chemical_list: D012997:Solvents; C400322:cytochrome P-450 CYP2C subfamily; D014241:Trichloroethylene; D003577:Cytochrome P-450 Enzyme System