title: Kinetics of naphthalene metabolism in target and non-target tissues of rodents and in nasal and airway microsomes from the Rhesus monkey.
abstract: Naphthalene produces species and cell selective injury to respiratory tract epithelial cells of rodents. In these studies we determined the apparent Km, Vmax, and catalytic efficiency (Vmax/Km) for naphthalene metabolism in microsomal preparations from subcompartments of the respiratory tract of rodents and non-human primates. In tissues with high substrate turnover, major metabolites were derived directly from naphthalene oxide with smaller amounts from conjugates of diol epoxide, diepoxide, and 1,2- and 1,4-naphthoquinones. In some tissues, different enzymes with dissimilar Km and Vmax appeared to metabolize naphthalene. The rank order of Vmax (rat olfactory epithelium>mouse olfactory epithelium>murine airways>>rat airways) correlated well with tissue susceptibility to naphthalene. The Vmax in monkey alveolar subcompartment was 2% that in rat nasal olfactory epithelium. Rates of metabolism in nasal compartments of the monkey were low. The catalytic efficiencies of microsomes from known susceptible tissues/subcompartments are 10 and 250 fold higher than in rat airway and monkey alveolar subcompartments, respectively. Although the strong correlations between catalytic efficiencies and tissue susceptibility suggest that non-human primate tissues are unlikely to generate metabolites at a rate sufficient to produce cellular injury, other studies showing high levels of formation of protein adducts support the need for additional studies.
authors.affiliation: Department of Molecular Biosciences, School of Veterinary Medicine, UC Davis, Davis, CA 95616, USA. arbuckpitt@ucdavis.edu
authors.forename: Alan
authors.initials: A
authors.lastname: Buckpitt
authors.forename: Dexter
authors.initials: D
authors.lastname: Morin
authors.forename: Shannon
authors.initials: S
authors.lastname: Murphy
authors.forename: Patricia
authors.initials: P
authors.lastname: Edwards
authors.forename: Laura
authors.initials: L
authors.lastname: Van Winkle
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004852:Epoxy Compounds / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008861:Microsomes / Q000378:metabolism*; D009281:Naphthalenes / Q000378:metabolism*; D009285:Naphthoquinones / Q000378:metabolism*; D009297:Nasal Mucosa / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004852:Epoxy Compounds; D009281:Naphthalenes; D009285:Naphthoquinones; C031721:naphthalene