Pulmonary biomarkers based on alterations in protein expression after exposure to arsenic.
OBJECTIVE
Environmental exposure to arsenic results in multiple adverse effects in the lung. Our objective was to identify potential pulmonary protein biomarkers in the lung-lining fluid of mice chronically exposed to low-dose As and to validate these protein changes in human populations exposed to As.


METHODS
Mice were administered 10 or 50 ppb As (sodium arsenite) in their drinking water for 4 weeks. Proteins in the lung-lining fluid were identified using two-dimensional gel electrophoresis (n = 3) or multidimensional protein identification technology (MUDPIT) (n = 2) coupled with mass spectrometry. Lung-induced sputum samples were collected from 57 individuals (tap water As ranged from ~ 5 to 20 ppb). Protein levels in sputum were determined by ELISA, and As species were analyzed in first morning void urine.


RESULTS
Proteins in mouse lung-lining fluid whose expression was consistently altered by As included glutathione-S-transferase (GST)-omega-1, contraspin, apolipoprotein A-I and A-IV, enolase-1, peroxiredoxin-6, and receptor for advanced glycation end products (RAGE). Validation of the putative biomarkers was carried out by evaluating As-induced alterations in RAGE in humans. Regression analysis demonstrated a significant negative correlation (p = 0.016) between sputum levels of RAGE and total urinary inorganic As, similar to results seen in our animal model.


CONCLUSIONS
Combinations of proteomic analyses of animal models followed by specific analysis of human samples provide an unbiased determination of important, previously unidentified putative biomarkers that may be related to human disease.
Lantz
R Clark
RC
Department of Cell Biology & Anatomy, and Southwest Environmental Health Science Center, University of Arizona, 1501 N. Campbell Avenue, Tucson, AZ 85724, USA. lantz@email.arizona.edu
Lynch
Brandon J
BJ
Boitano
Scott
S
Poplin
Gerald S
GS
Littau
Sally
S
Tsaprailis
George
G
Burgess
Jefferey L
JL
D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism*; D004195:Disease Models, Animal; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D013058:Mass Spectrometry; D051379:Mice; D011506:Proteins / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D012016:Reference Values; D013183:Sputum / Q000737:chemistry; D014881:Water Supply
D015415:Biomarkers; D004785:Environmental Pollutants; D011506:Proteins; D001151:Arsenic