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ToxSci Advance Access published online on March 31, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh124
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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Received November 7, 2003; accepted February 29, 2004
© 2004 Toxicological Sciences © Society of Toxicology 2004; all rights reserved.

Environmental Toxicology

Induction of Cetacean Cytochrome P4501A1 by {beta}-Naphthoflavone Exposure of Skin Biopsy Slices

Céline A. J. Godard 1*, Roxanna M. Smolowitz 2, Joanna Y. Wilson 3, Roger S. Payne 4, and John J. Stegeman 5

1 Woods Hole Oceanographic Institution, Biology Department, 45 Water Street, Woods Hole, MA 02543, USA; Ocean Alliance, Lincoln, MA 01773, USA
2 Marine Biological Laboratory, Woods Hole, MA 02543, USA
3 Woods Hole Oceanographic Institution, Woods Hole, MA 02543, USA
4 Ocean Alliance, Lincoln, MA 01773, USA
5 Biology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543, USA

* To whom correspondence should be addressed. E-mail: cgodard{at}whoi.edu.


  Abstract

Marine mammals can accumulate environmental contaminants in their blubber at concentrations harmful to laboratory animals. Induction of the cytochrome P450 1A1 (CYP1A1) enzyme is widely used as a biomarker of exposure and molecular effects in animal species, yet the validity of this biomarker has not been established in marine mammals. In vivo studies are generally precluded in these protected species but skin biopsies (epidermis and dermis) can be collected in a minimally invasive way. We developed an in vitro assay using skin biopsy slices to examine CYP1A1 protein induction in marine mammals in response to chemical exposure. Skin biopsies from sperm whale (Physeter macrocephalus) were exposed for 24 hr to {beta}-naphthoflavone (BNF), a prototypical CYP1A1 inducer and CYP1A1 induction was detected by immunochemical staining in endothelial cells, smooth muscle cells and fibroblasts. Biopsy slices were exposed to a range of BNF concentrations (0.6-600 µM) and a significant concentration-effect relationship was observed in both endothelial and smooth muscle cells (p=0.05). This is the first study using skin biopsy slices to examine exposure of cetacean tissue to a CYP1A1 inducer. It demonstrates a causal relationship between chemical exposure and CYP1A1 induction and therefore validates the use of CYP1A1 expression in skin biopsies as a biomarker in cetaceans. Our protocol can be adapted to the investigation of chemicals, mixtures, concentrations, incubation times or biological endpoints of choice. This should prove particularly relevant for these and other protected species that cannot be studied in the laboratory.

Key Words: marine mammal, CYP1A1, skin, {beta}-naphthoflavone, sperm whale, endothelium, dose-response .


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