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

R. Michael Baldwin, William T. Jewell, Michelle V. Fanucchi, Charles Plopper, Alan R Buckpitt

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)127-136
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Volume309
Issue number1
DOIs
StatePublished - Apr 2004
Externally publishedYes

Fingerprint

Macaca mulatta
Nose
Rodentia
Lung
Liver
Bronchioles
Kidney
Olfactory Mucosa
Proteins
Epoxy Compounds
Wounds and Injuries
Lung Injury
Trachea
Respiratory System
Cytochrome P-450 Enzyme System
Primates
Necrosis
Messenger RNA
naphthalene

ASJC Scopus subject areas

  • Pharmacology

Cite this

Comparison of Pulmonary/Nasal CYP2F Expression Levels in Rodents and Rhesus Macaque. / Baldwin, R. Michael; Jewell, William T.; Fanucchi, Michelle V.; Plopper, Charles; Buckpitt, Alan R.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 309, No. 1, 04.2004, p. 127-136.

Research output: Contribution to journalArticle

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