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Comparison of nasal proteins adducted by reactive metabolites of naphthalene (NA) in rat and rhesus macaque using 2 dimensional gel electrophoresis and MALDI TOF/TOF
Author(s) -
Shields Christina E DeStefano,
Morin Dexter,
Buckpitt Alan
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1131.9
Subject(s) - olfactory epithelium , gel electrophoresis , olfactory mucosa , chemistry , microbiology and biotechnology , macaque , carcinogen , biochemistry , biology , olfactory system , receptor , paleontology , neuroscience
NA is a volatile pollutant classified by NTP as a ‘reasonably anticipated human carcinogen’ based on concentration‐dependent, rare olfactory epithelial neuroblastomas and respiratory (nasal) epithelial adenomas in rats (NTP 2000). However, epidemiologic studies have not provided a convincing link between exposure and cancer. Reactive metabolites of NA bind covalently to proteins in target cells; good correlations between adducted protein levels and injury have been observed (Drug Metab Rev 34:791, 2002). Accordingly, these studies compared adducted proteins in nasal epithelium of rats and rhesus macaques to develop biomarkers mechanistically associated with toxicity which could be applied to human populations. Rat and monkey nasal tissues were incubated with 14 C ‐NA, proteins were resolved by 2D gel electrophoresis, and labeled proteins were imaged and subsequently identified. The adducted protein patterns between rat and rhesus macaque are remarkably similar. 45 adducted proteins identified in rat olfactory incubations include those involved in cell structure, transcription, protein synthesis/folding, ATP synthesis, and cell signaling; similar work is ongoing in monkeys. These studies suggest that several of these adducts may be good biomarker targets for assessing the potential for NA toxicity in humans. Supported by EPRI, NIEHS 04311, 04699 and RR00169.