title: Styrene-oxide N-terminal valine haemoglobin adducts in reinforced plastic workers: possible influence of genetic polymorphism of drug-metabolising enzymes.
abstract: Styrene is one of the most important organic chemicals used worldwide. In humans, styrene metabolism involves oxidation by cytochrome P450 monooxygenases (CYPs) to styrene-7,8-oxide, an epoxide thought to be responsible for the genotoxic effects of styrene exposure, and detoxification by means of epoxide hydrolase (mEH) and glutathione S-transferases (GSTs). The objective of this study was to investigate if genetic polymorphisms of metabolic enzymes modulate the level of urinary styrene metabolites and styrene oxide adducts with N-terminal valine of human globin (SO-Hb) in 75 workers occupationally exposed to styrene and 77 unexposed controls. The mean air concentration of styrene in the breathing zone of workers (30.4ppm) was higher than the threshold limit value of 20ppm recommended by the American Conference of Governmental Industrial Hygienists (ACGIH), and the biological exposure index adopted by the ACGIH for exposure to styrene prior to the next shift (MA+PGA=400mg/g creatinine) was exceeded, indicating that styrene exposure for this group of workers was higher than recommended. A highly significant correlation was observed between styrene concentration in the breathing zone and the MA+PGA in urine of workers (r=0.85, P<0.001). The levels of SO-Hb adducts in exposed workers were significantly increased as compared with controls, although no difference was observed between subjects stratified as high and medium exposure categories based on MA+PGA excretion. Regarding the effect of the genetic polymorphisms we found that the level of SO-Hb adducts might be modulated by the predicted mEH enzymatic activity in the exposed workers. From our data we conclude that SO-Hb adduct measurement is a complementary method to MA+PG measurement for assessing exposure to styrene at occupational and environmental levels, which reflects a more extensive exposure period.
authors.affiliation: National Institute of Health, Centre of Occupational and Environmental Health, Praça Coronel Pacheco, 15, 4050-453 Porto, Portugal. Electronic address: jpft12@gmail.com.
authors.forename: J P
authors.initials: JP
authors.lastname: Teixeira
authors.affiliation: Faculty of Medical Sciences UNL, Department of Genetics, Lisbon, Portugal.
authors.forename: J
authors.initials: J
authors.lastname: Gaspar
authors.affiliation: National Institute of Health, Centre of Occupational and Environmental Health, Praça Coronel Pacheco, 15, 4050-453 Porto, Portugal.
authors.forename: J
authors.initials: J
authors.lastname: Roma-Torres
authors.affiliation: National Institute of Health, Centre of Occupational and Environmental Health, Praça Coronel Pacheco, 15, 4050-453 Porto, Portugal.
authors.forename: S
authors.initials: S
authors.lastname: Silva
authors.affiliation: National Institute of Health, Centre of Occupational and Environmental Health, Praça Coronel Pacheco, 15, 4050-453 Porto, Portugal.
authors.forename: C
authors.initials: C
authors.lastname: Costa
authors.affiliation: Cancer Biomarkers and Prevention Group, University of Leicester, UK.
authors.forename: J
authors.initials: J
authors.lastname: Roach
authors.affiliation: National Institute of Health, Centre of Occupational and Environmental Health, Praça Coronel Pacheco, 15, 4050-453 Porto, Portugal.
authors.forename: O
authors.initials: O
authors.lastname: Mayan
authors.affiliation: Faculty of Medical Sciences UNL, Department of Genetics, Lisbon, Portugal.
authors.forename: J
authors.initials: J
authors.lastname: Rueff
authors.affiliation: Cancer Biomarkers and Prevention Group, University of Leicester, UK.
authors.forename: P B
authors.initials: PB
authors.lastname: Farmer
mesh_terms: D000328:Adult; D000395:Air Pollutants, Occupational / Q000493:pharmacokinetics / Q000633:toxicity*; D015415:Biomarkers / Q000032:analysis / Q000652:urine; D002617:Chemical Industry; D004798:Enzymes / Q000235:genetics*; D004852:Epoxy Compounds / Q000032:analysis* / Q000378:metabolism; D005260:Female; D006038:Glyoxylates / Q000652:urine; D006454:Hemoglobins / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D008297:Male; D008333:Mandelic Acids / Q000652:urine; D016273:Occupational Exposure / Q000009:adverse effects / Q000032:analysis; D011110:Polymorphism, Genetic; D020058:Styrene / Q000493:pharmacokinetics / Q000633:toxicity*; D014633:Valine / Q000032:analysis* / Q000378:metabolism; D017132:Workplace / Q000592:standards
chemical_list: D000395:Air Pollutants, Occupational; D015415:Biomarkers; D004798:Enzymes; D004852:Epoxy Compounds; D006038:Glyoxylates; D006454:Hemoglobins; D008333:Mandelic Acids; C012482:phenylglyoxylic acid; D020058:Styrene; C013690:styrene oxide; D014633:Valine; C037938:mandelic acid