title: Comparative chronic liver toxicity of benzo[a]pyrene in two populations of the atlantic killifish (Fundulus heteroclitus) with different exposure histories.
abstract: BACKGROUND
  The Atlantic Wood Industries Superfund site on the Elizabeth River (ER) in Portsmouth, Virginia, is contaminated with polycyclic aromatic hydrocarbons (PAHs) derived from creosote. Embryos and larvae of ER killifish (Fundulus heteroclitus) are refractory to the induction of enzymes regulated by the aryl hydrocarbon receptor including cytochrome P4501A (CYP1A) and are resistant to PAH-induced lethality and teratogenicity. However, adult ER killifish show a greater prevalence of hepatic and pancreatic tumors compared with those from reference sites.
  
  
  OBJECTIVE
  We used controlled laboratory studies to determine if ER killifish are more or less sensitive to PAH-induced chronic hepatic toxicity than killifish from an uncontaminated site.
  
  
  METHODS
  Larvae from the ER and a reference site on King's Creek (KC) were subjected to two 24-hr aqueous exposures of benzo[a]pyrene (BaP; 0-400 µg/L). At various time points, larvae were analyzed for CYP1A activity, BaP concentrations, nuclear and mitochondrial DNA damage, and liver pathology.
  
  
  RESULTS
  CYP1A activity was induced by BaP in KC but not ER larvae, and KC larvae demonstrated a greater reduction in whole-body concentrations of BaP over time. Mitochondrial and nuclear DNA lesion frequency increased significantly in BaP-exposed KC larvae, but not in ER larvae. Nine months postexposure, KC juveniles exhibited significantly more hepatic foci of cellular alteration and only KC juveniles developed hepatocellular carcinomas.
  
  
  CONCLUSIONS
  In addition to acquiring the heritable resistance to the acute teratogenic effects of PAHs, ER fish appear to have concomitantly developed resistance to chronic effects, including cancer.
authors.affiliation: Nicholas School of the Environment, Duke University, Durham, North Carolina 27708, USA.
authors.forename: Lauren P
authors.initials: LP
authors.lastname: Wills
authors.forename: Dawoon
authors.initials: D
authors.lastname: Jung
authors.forename: Kara
authors.initials: K
authors.lastname: Koehrn
authors.forename: Shiqian
authors.initials: S
authors.lastname: Zhu
authors.forename: Kristine L
authors.initials: KL
authors.lastname: Willett
authors.forename: David E
authors.initials: DE
authors.lastname: Hinton
authors.forename: Richard T
authors.initials: RT
authors.lastname: Di Giulio
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D004781:Environmental Exposure; D023781:Fundulidae; D008099:Liver / Q000187:drug effects*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D014874:Water Pollutants, Chemical; D001564:Benzo(a)pyrene