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Biological monitoring and the influence of genetic polymorphism of As3MT and GSTs on distribution of urinary arsenic species in occupational exposure workers.

Janasik B, Reszka E, Stanislawska M, Wieczorek E, Fendler W, Wasowicz W - Int Arch Occup Environ Health (2014)

Bottom Line: 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).Nevertheless, further studies investigating genetic polymorphism in occupational conditions are required.

View Article: PubMed Central - PubMed

Affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lodz, Poland, beatajan@imp.lodz.pl.

ABSTRACT

Purpose: 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.

No MeSH data available.


Related in: MedlinePlus

Scheme of oxidative methylation of arsenite (Reichard and Puga 2010). As3MT arsenic (+3 oxidation state) methyltransferase, GSTO glutathione S-transferase Ω
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Fig1: Scheme of oxidative methylation of arsenite (Reichard and Puga 2010). As3MT arsenic (+3 oxidation state) methyltransferase, GSTO glutathione S-transferase Ω

Mentions: Arsenic (As) is a significant global environmental toxicant and As contamination of soil, and drinking water is a problem threatening human health all over the world. Humans are exposed to As through the intake of air, food and water and occupational exposure occurs in several industries including gold mining and smelting operations. It is well established that chronic exposure to As is associated with skin, lung and bladder cancers (IARC 1987; Helene et al. 2007; Järup et al. 1989; Lauwerys and Hoet 2001) as well as vascular diseases and hepatotoxicity (NRC 2001). The biotransformation pathway of As consists of several change in the oxidative state, oxidative methylation, producing at least four metabolites (Fig. 1). Inorganic As (iAs) is metabolized by reduction in pentavalent iAs to the trivalent form (AsIII), followed by oxidative methylation to monomethylated As (MMA), further reduction from pentavalent MMA to trivalent one and final methylation to dimethylated As (DMA) (Vahter 1999, 2002). Recently, a reductive methylation pathway has also been described (Tseng 2009). Methylated As is less toxic than the inorganic form, and methylation has been considered to be a detoxification reaction. However, recent studies have shown that methylated AsIII is more cytotoxic and genotoxic than arsenate and arsenite (Styblo et al. 2000). Following arsenic exposure, 40–60 % of arsenic intake is eliminated through urine. It should also be mentioned that the majority of the environmentally exposed population groups studied so far have on average 10–30 % of inorganic As, 10–20 % of MMA and 60–70 % of DMA in urine, but considerable inter-individual variations have been observed, which may be a result of genetic polymorphism in the methylation capacity of arsenic (Vahter 1999).Fig. 1


Biological monitoring and the influence of genetic polymorphism of As3MT and GSTs on distribution of urinary arsenic species in occupational exposure workers.

Janasik B, Reszka E, Stanislawska M, Wieczorek E, Fendler W, Wasowicz W - Int Arch Occup Environ Health (2014)

Scheme of oxidative methylation of arsenite (Reichard and Puga 2010). As3MT arsenic (+3 oxidation state) methyltransferase, GSTO glutathione S-transferase Ω
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4508369&req=5

Fig1: Scheme of oxidative methylation of arsenite (Reichard and Puga 2010). As3MT arsenic (+3 oxidation state) methyltransferase, GSTO glutathione S-transferase Ω
Mentions: Arsenic (As) is a significant global environmental toxicant and As contamination of soil, and drinking water is a problem threatening human health all over the world. Humans are exposed to As through the intake of air, food and water and occupational exposure occurs in several industries including gold mining and smelting operations. It is well established that chronic exposure to As is associated with skin, lung and bladder cancers (IARC 1987; Helene et al. 2007; Järup et al. 1989; Lauwerys and Hoet 2001) as well as vascular diseases and hepatotoxicity (NRC 2001). The biotransformation pathway of As consists of several change in the oxidative state, oxidative methylation, producing at least four metabolites (Fig. 1). Inorganic As (iAs) is metabolized by reduction in pentavalent iAs to the trivalent form (AsIII), followed by oxidative methylation to monomethylated As (MMA), further reduction from pentavalent MMA to trivalent one and final methylation to dimethylated As (DMA) (Vahter 1999, 2002). Recently, a reductive methylation pathway has also been described (Tseng 2009). Methylated As is less toxic than the inorganic form, and methylation has been considered to be a detoxification reaction. However, recent studies have shown that methylated AsIII is more cytotoxic and genotoxic than arsenate and arsenite (Styblo et al. 2000). Following arsenic exposure, 40–60 % of arsenic intake is eliminated through urine. It should also be mentioned that the majority of the environmentally exposed population groups studied so far have on average 10–30 % of inorganic As, 10–20 % of MMA and 60–70 % of DMA in urine, but considerable inter-individual variations have been observed, which may be a result of genetic polymorphism in the methylation capacity of arsenic (Vahter 1999).Fig. 1

Bottom Line: 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).Nevertheless, further studies investigating genetic polymorphism in occupational conditions are required.

View Article: PubMed Central - PubMed

Affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lodz, Poland, beatajan@imp.lodz.pl.

ABSTRACT

Purpose: 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.

No MeSH data available.


Related in: MedlinePlus