title: 3-chlorotyrosine and 3,5-dichlorotyrosine as biomarkers of respiratory tract exposure to chlorine gas.
abstract: 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).
authors.affiliation: The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709-2137, USA. MSochaski@thehamner.org
authors.forename: Mark A
authors.initials: MA
authors.lastname: Sochaski
authors.forename: Annie M
authors.initials: AM
authors.lastname: Jarabek
authors.forename: John
authors.initials: J
authors.lastname: Murphy
authors.forename: Melvin E
authors.initials: ME
authors.lastname: Andersen
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002138:Calibration; D002619:Chemical Warfare Agents / Q000032:analysis / Q000378:metabolism; D002713:Chlorine / Q000008:administration & dosage / Q000032:analysis* / Q000378:metabolism; D004781:Environmental Exposure / Q000032:analysis; D004784:Environmental Monitoring / Q000379:methods*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D009297:Nasal Mucosa / Q000737:chemistry / Q000378:metabolism; D009831:Olfactory Mucosa / Q000737:chemistry / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D020545:Respiratory Mucosa / Q000737:chemistry* / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis
chemical_list: D015415:Biomarkers; D002619:Chemical Warfare Agents; D011506:Proteins; D014443:Tyrosine; D002713:Chlorine; C408691:3,5-dichlorotyrosine; C087259:3-chlorotyrosine