Naphthalene Toxicity in Mice and Aryl Hydrocarbon Receptor-mediated Cyps.
From: Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati, Cincinnati, OH 45267-0056, USA. marybeth.genter@uc.edu
Biochemical and biophysical research communications
- Publish Date: Sep 2006
- ISSN: 0006-291X
- Volume: 348
- Issue: 1
- Pages: 120-3
- Medium: Print
- Language: English
- Citation (JAMA): Genter Mary Beth, Marlowe Jennifer, Kevin Kerzee J, et al. Naphthalene Toxicity in Mice and Aryl Hydrocarbon Receptor-mediated Cyps.. Biochem. Biophys. Res. Commun. Sep 2006;348:120-3
Abstract
Naphthalene (NP) has been designated a “reasonably anticipated human carcinogen” because of positive responses in carcinogenicity bioassays in rodents. Whereas CYP2F enzymes are widely regarded as responsible for NP bioactivation, other metabolic enzymes — including CYP1A1 and CYP1A2 — produce NP-1,2-oxide in vitro. We investigated the role of these aryl hydrocarbon receptor (AHR)-mediated enzymes in NP toxicity in two ways. First, NP was assessed for the ability to activate transcription via the AHR in an in vitro luciferase reporter assay and was found to have no activity. Second, mice deficient in AHR, CYP1A1 or CYP1A2 were dosed with NP alone, or following pretreatment with the CYP2F inhibitor 5-phenyl-1-pentyne. None of the knockout mice were protected from olfactory toxicity of NP. In contrast, CYP1A1- and CYP1A2-null mice pretreated with 5-phenyl-1-pentyne exhibited no NP olfactory toxicity. These results suggest that AHR-mediated enzymes do not contribute significantly to NP bioactivation in the intact animal.
Mesh Headings (Keywords): Alkynes, Animals, Benzene Derivatives, Cytochrome P-450 CYP1A1, Cytochrome P-450 CYP1A2, Cytochrome P-450 Enzyme System, Gene Expression Regulation, Humans, Mice, Mice, Knockout, Naphthalenes, Receptors, Aryl Hydrocarbon, Signal Transduction, Turbinates
Check for Full Text / PubMed Unique Identifier (PMID): 16876762
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