Induction of cetacean cytochrome P4501A1 by β-naphthoflavone exposure of skin biopsy slices Short title (40 characters max): Inducibility of cetacean cytochrome P4501A1
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 no...
| Main Authors: | , , , , |
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| Other Authors: | |
| Format: | Text |
| Language: | English |
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| Online Access: | http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.326.4267 http://www.pbs.org/odyssey/voyage/oa_dosing_study.pdf |
| Summary: | 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 β-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 concentrationeffect 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 |
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