title: Biological monitoring and the influence of genetic polymorphism of As3MT and GSTs on distribution of urinary arsenic species in occupational exposure workers.
abstract: OBJECTIVE
  To examine the differences in urinary arsenic metabolism patterns in men affected by occupational exposure, we performed a study on 149 participants—workers of a copper mill and 52 healthy controls without occupational exposure. To elucidate the role of genetic factors in arsenic (As) metabolism, we studied the associations of six polymorphisms: As3MT Met287Thr (T>C) in exon 9; As3MT A>G in 5'UTR; As3MT C>G in intron 6; As3MT T>G in intron 1; GSTP1 Ile105Val and GSTO2 T>C.
  
  
  METHODS
  Air samples were collected using individual samplers during work shift. Urine samples were analyzed for total arsenic and arsenic chemical forms (As(III); As(V), MMA, DMA, AsB) using HPLC-ICP-MS. A specific polymerase chain reaction was done for the amplification of exons and flanking regions of As3MT and GSTs.
  
  
  RESULTS
  The geometric mean arsenic concentrations in the air were 27.6 ± 4.9 µg/m(3). A significant correlation (p < 0.05) was observed between arsenic in air and sum of iAs +MMA and iAs. As3MT (rs3740400) GG homozygotes showed significantly (p < 0.05) higher %iAs (21.8 ± 2.0) in urine than GC+CC heterozygotes (16.0 ± 2.1). A strong association between the gene variants and As species in urine was observed for GSTO2 (rs156697) polymorphism.
  
  
  CONCLUSIONS
  The findings of the study point out that the concentration of iAs or the sum of iAs + MMA in urine can be a reliable biological indicator of occupational exposure to arsenic. This study demonstrates that As3MT and/or GSTs genotype may influence As metabolism. Nevertheless, further studies investigating genetic polymorphism in occupational conditions are required.
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lodz, Poland, beatajan@imp.lodz.pl.
authors.forename: Beata
authors.initials: B
authors.lastname: Janasik
authors.forename: Edyta
authors.initials: E
authors.lastname: Reszka
authors.forename: Magdalena
authors.initials: M
authors.lastname: Stanislawska
authors.forename: Edyta
authors.initials: E
authors.lastname: Wieczorek
authors.forename: Wojciech
authors.initials: W
authors.lastname: Fendler
authors.forename: Wojciech
authors.initials: W
authors.lastname: Wasowicz
mesh_terms: D000328:Adult; D001151:Arsenic / Q000652:urine*; D003300:Copper; D004784:Environmental Monitoring / Q000379:methods*; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008669:Metallurgy; D008780:Methyltransferases / Q000235:genetics*; D008875:Middle Aged; D016273:Occupational Exposure / Q000032:analysis; D011044:Poland; D011110:Polymorphism, Genetic
chemical_list: D003300:Copper; D008780:Methyltransferases; C505756:AS3MT protein, human; C492569:GSTO2 protein, human; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D001151:Arsenic