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3-Chlorotyrosine and 3,5-Dichlorotyrosine as biomarkers of respiratory tract exposure to chlorine gas
Sochaski, M., J. Murphy, A. M. JARABEK, AND M. Anderson. 3-Chlorotyrosine and 3,5-Dichlorotyrosine as biomarkers of respiratory tract exposure to chlorine gas. JOURNAL OF ANALYTICAL TOXICOLOGY. Preston Publications Incorporated, Niles, IL, 32(1):99-105, (2008).
Modification of tyrosine by reactive chlorine can produce both 3-chlorotyrosine (CY) and 3,5-dichlorotyrosine (dCY). Both of these amino acids have proven to be promising biomarkers for assessing the extent of myeloperoxidase-catalyzed chlorine stress in a number of adverse physiological conditions. To date, there has been no application of these biomarkers for determining the extent of exposure to environmentally present gaseous chlorinating chemicals. In this manuscript, we present a method using selective ion monitoring gas chromatography for the simultaneous analysis of both CY and dCY in nasal tissue excised from Fisher 344 rats exposed to varying concentrations of chlorine gas. Using this method, we were able to demonstrate the following: 1. a dose-dependent increase in the conversion of tyrosine to CY and dCY in the respiratory epithelium tissue; 2. preferential formation of CY and dCY in the respiratory and transitional epithelium versus the olfactory epithelium of the nasal cavity of the rat; and 3. similar rates of formation for CY and dCY when exposed to chlorine gas based on a strong [CY] versus [dCY] correlation (slope = 1.001, r(2) = 0.912).
Chlorotyrosines have been demonstrated to be stable markers of oxidative stress secondary to inflammation, especially from hypochlorous acid (HOCI) in polymorphonuclear (PNIN) leukocytes. Because chlorine immediately hydrolyzes to HOCI in tissues, this technique to track3-chlorotyrosine and 3,5-dichlorotyrosine in nasal tissues was developed to serve as a dosimeter for acute chlorine exposures.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
EXPERIMENTAL TOXICOLOGY DIVISION