QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.103.062901v1 309/1/127    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Baldwin, R. M. Articles by Buckpitt, A. R. Search for Related Content PubMed PubMed Citation Articles by Baldwin, R. M. Articles by Buckpitt, A. R.

TOXICOLOGY

Comparison of Pulmonary/Nasal CYP2F Expression Levels in Rodents and Rhesus Macaque

Departments of Molecular Biosciences (R.M.B., A.R.B.) and Anatomy, Physiology, and Cell Biology (M.V.F., C.G.P.), School of Veterinary Medicine, and the Molecular Structure Facility (W.T.J.), University of California, Davis, California

Naphthalene is a ubiquitous environmental contaminant that results in dose-dependent and tissue-, species-, and cell-selective necrosis of murine Clara cells upon exposure. Naphthalene is metabolized by CYP2F to a 1,2-epoxide, the first and obligate step in events leading to cytotoxicity. The studies reported here examine the relationship between levels of transcript (mRNA) and CYP2F protein in the respiratory tract of rodents with tissue susceptibility to injury. In both mice and rats, the lung contains more CYP2F transcript than liver; levels in kidney were undetectable. Mice expressed 4- and 8-fold greater CYP2F transcript in lung and liver tissue, respectively, than rats. Quantitative immunoblot blot analysis of CYP2F in airway subcompartments revealed mice to have 30- (minor daughters/terminal bronchioles), 20- (major daughter), 40- (trachea), and 6- (parenchyma) fold higher levels of CYP2F protein than rats. Within the lungs of both rodent species, the highest CYP2F expression was found in the distal airways. The kidney contained undetectable amounts of CYP2F; multiple immunoreactive bands in liver precluded quantification. The olfactory epithelium contains the greatest amount of cytochrome P450 protein of all tissues studied in the rat, consistent with the observed pattern of in vivo injury. Overall, these studies in rodents demonstrate a strong association between CYP2F expression levels and susceptibility to naphthalene-induced cytotoxicity. Of all primate tissues studied, only the nasal ethmoturbinates contain quantifiable amounts of CYP2F, roughly 10- and 20-fold less than the corresponding tissues in rats and mice, respectively. These results suggest that rhesus macaques may be refractory to naphthalene-induced pulmonary injury.

Address correspondence to: Dr. R. Michael Baldwin, Veterinary Medicine, Molecular Biosciences, 1311 Haring Hall, University of California Davis, Davis, CA 95616. E-mail: rmbaldwin{at}ucdavis.edu

This article has been cited by other articles:

				K. C. Day, C. G. Plopper, and M. V. Fanucchi Age-specific pulmonary cytochrome P-450 3A1 expression in postnatal and adult rats Am J Physiol Lung Cell Mol Physiol, July 1, 2006; 291(1): L75 - L83. [Abstract] [Full Text] [PDF]

				P.-G. Forkert, R. M. Baldwin, B. Millen, L. H. Lash, D. A. Putt, M. A. Shultz, and K. S. Collins PULMONARY BIOACTIVATION OF TRICHLOROETHYLENE TO CHLORAL HYDRATE: RELATIVE CONTRIBUTIONS OF CYP2E1, CYP2F, AND CYP2B1 Drug Metab. Dispos., October 1, 2005; 33(10): 1429 - 1437. [Abstract] [Full Text] [PDF]

				R. M. Baldwin, M. A. Shultz, and A. R. Buckpitt Bioactivation of the Pulmonary Toxicants Naphthalene and 1-Nitronaphthalene by Rat CYP2F4 J. Pharmacol. Exp. Ther., February 1, 2005; 312(2): 857 - 865. [Abstract] [Full Text] [PDF]

				B. Boland, C. Y. Lin, D. Morin, L. Miller, C. Plopper, and A. Buckpitt Site-Specific Metabolism of Naphthalene and 1-Nitronaphthalene in Dissected Airways of Rhesus Macaques J. Pharmacol. Exp. Ther., August 1, 2004; 310(2): 546 - 554. [Abstract] [Full Text] [PDF]