Formation of covalently bound protein adducts from the cytotoxicant naphthalene in nasal epithelium: species comparisons.

ABSTRACT: BACKGROUND: Naphthalene is a volatile hydrocarbon that causes dose-, species-, and cell type-dependent cytotoxicity after acute exposure and hyperplasia/neoplasia after lifetime exposures in rodents. Toxicity depends on metabolic activation, and reactive metabolite binding correlates with tissue and site susceptibility. OBJECTIVES: We compared proteins adducted in nasal epithelium from rats and rhesus macaques in vitro. METHODS: Adducted proteins recovered from incubations of nasal epithelium and 14C-naphthalene were separated by two-dimensional (2D) gel electrophoresis and imaged to register radioactive proteins. We identified proteins visualized by silver staining on complementary non-radioactive gels by peptide mass mapping. RESULTS: The levels of reactive metabolite binding in incubations of rhesus ethmo-turbinates and maxillo-turbinates are similar to those in incubations of target tissues, including rat septal/-olfactory regions and murine dissected airway incubations. We identified 40 adducted spots from 2D gel separations of rat olfactory epithelial proteins; 22 of these were non-redundant. In monkeys, we identified 19 spots by mass spectrometry, yielding three non-redundant identifications. Structural proteins (actin/tubulin) were prominent targets in both species. CONCLUSIONS: In this study we identified potential target proteins that may serve as markers closely associated with toxicity. The large differences in previously reported rates of naphthalene metabolism to water-soluble metabolites in dissected airways from mice and monkeys are not reflected in similar differences in covalent adduct formation in the nose. This raises concerns that downstream metabolic/biochemical events are very similar between the rat, a known target for naphthalene toxicity and tumorigenicity, and the rhesus macaque, a species similar to the human.

SUBMITTER: DeStefano-Shields C 

PROVIDER: S-EPMC2866680 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature