Comparative chronic liver toxicity of benzo[a]pyrene in two populations of the atlantic killifish (Fundulus heteroclitus) with different exposure histories.


Journal Article

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.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.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.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.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.

Full Text

Duke Authors

Cited Authors

  • Wills, LP; Jung, D; Koehrn, K; Zhu, S; Willett, KL; Hinton, DE; Di Giulio, RT

Published Date

  • October 2010

Published In

Volume / Issue

  • 118 / 10

Start / End Page

  • 1376 - 1381

PubMed ID

  • 20501349

Pubmed Central ID

  • 20501349

Electronic International Standard Serial Number (EISSN)

  • 1552-9924

International Standard Serial Number (ISSN)

  • 0091-6765

Digital Object Identifier (DOI)

  • 10.1289/ehp.0901799


  • eng