Formation of Covalently Bound Protein Adducts from the Cytotoxicant Naphthalene in Nasal Epithelium: Species Comparisons
| Autor: | Alan R. Buckpitt, Christina DeStefano-Shields, Dexter Morin |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Lung Diseases
Male Health Toxicology and Mutagenesis Metabolite Cell Mucous membrane of nose In Vitro Techniques Naphthalenes Biology Rats Sprague-Dawley Mice species comparisons chemistry.chemical_compound Species Specificity medicine Animals Humans rat Cytotoxicity Naphthalene Research reactive metabolites naphthalene Public Health Environmental and Occupational Health Proteins protein adducts Hyperplasia medicine.disease Macaca mulatta nasal epithelium Epithelium Rats Disease Models Animal Nasal Mucosa medicine.anatomical_structure chemistry Biochemistry Covalent bond Environmental Pollutants Female monkey |
| Zdroj: | Environmental Health Perspectives |
| ISSN: | 1552-9924 0091-6765 |
| Popis: | 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 nonradioactive gels by peptide mass mapping. Results The levels of reactive metabolite binding in incubations of rhesus ethmoturbinates and maxilloturbinates 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 nonredundant. In monkeys, we identified 19 spots by mass spectrometry, yielding three nonredundant 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. |
| Databáze: | OpenAIRE |
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