GSTM1 polymorphism and styrene metabolism: insights from an acute accidental exposure.
Two workers were accidentally exposed to unusually high styrene concentrations (>1000 ppm) for about 30 min. In addition to the main styrene metabolites, mandelic acid (MA) and phenylglyoxylic acid (PGA), other minor metabolites, including specific mercapturic acids, (R,R)- and (S,R)-N-acetyl-S-(1-phenyl-2-hydroxyethyl)-L-cysteine [(R,R)-M1 and (S,R)-M1] and (R,R)- and (S,R)-N-acetyl-S-(2-phenyl-2-hydroxyethyl)-L-cysteine [(R,R)-M2 and (S,R)-M2], 4-vinylphenol-glucuronide and -sulfate, and phenylglycine, were determined by Liquid Chromatography Electrospray Tandem Mass Spectrometry (LC-ESI-MS/MS) in urine samples collected 12, 24, 36, 48, 75 and 99 h after the episode. The genotypes of microsomal epoxide hydrolase, glutathione-S-transferases M1-1 (GSTM1), T1-1 (GSTT1) and P1-1 (GSTP1) were characterized by PCR-based methods. The two subjects showed similar peak levels of MA and PGA, as well as 4-vinylphenol conjugates, whereas mercapturic acids were five times higher in the subject bearing the GSTM1pos than in the GSTM1null subject. Also, relative proportions of diasteroisomers of mercapturic acids were influenced by the GSTM1 polymorphism.
Laboratory of Industrial Toxicology, Department of Clinical Medicine, Nephrology and Health Sciences, University of Parma Medical School, via Gramsci 14, 43100 Parma, Italy. paola.manini@unipr.it
Paola
P
Manini
Giuseppe
G
De Palma
Paola
P
Mozzoni
Roberta
R
Andreoli
Diana
D
Poli
Enrico
E
Bergamaschi
Innocente
I
Franchini
Antonio
A
Mutti
D000059:Accidents; D000328:Adult; D002853:Chromatography, Liquid; D004247:DNA / Q000032:analysis; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D019570:Inhalation Exposure / Q000032:analysis; D008875:Middle Aged; D016273:Occupational Exposure / Q000032:analysis*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism; D020058:Styrene / Q000493:pharmacokinetics*
D004247:DNA; D005982:Glutathione Transferase; D020058:Styrene