Metabolic profile in workers occupationally exposed to arsenic: role of GST polymorphisms.
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AbstractArsenic is a well-known human carcinogen with a ubiquitous distribution in the natural environment. Chronic exposure to inorganic arsenic involves a biotransformation process that leds to the main excretion of organic methylated metabolites, such as monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), as well as the parental inorganic species. Interindividual variation in arsenic metabolism has been extensively reported, and polymorphisms in genes involved in such process could be related to changes in the arsenic excretion profile and the response to chronic exposures. Our analysis of the metabolic profiles in three groups of workers exposed to different arsenic exposure levels showed high amounts of inorganic arsenic and MMA in the most-exposed workers versus the least-exposed workers, in whom high amounts of DMA were observed. With respect to the role of different genetic polymorphisms in the glutathione S-transferase (GST) genes in the modulation of the urinary profiles, for the overall population only a tendency was just observed between GSTM1 null and MMA excretion as well as between GSTP1 val/val and DMA excretion.
CitationMetabolic profile in workers occupationally exposed to arsenic: role of GST polymorphisms. 2006, 48 (3):334-41 J. Occup. Environ. Med.
DescriptionBiomarkers of exposure & early effects: field studiesBiomarker:MMA, DMAExposure/effect represented:arsenicStudy design:cross-sectionalStudy size:207 workers (105 exposed, 52 internal control, 50 external control)Analytical technique:ICP/MS, HPLCTissue/biological material/sample size:9ml blood samples, 125 ml urineInter-individual variation:table 4Relationship with exposure or effect of interest (including dose-response):As(inorg.) for exposed 19.11+/-1.46, internal control 19.97+/-1.49, external control 13.47+/-1.25MMA for exposed 12.85+/-0.62, internal control 16.55+/-0.89, external control 10.33+/-1.42DMA for exposed 68.04+/-1.32, internal control 66.5+/-1.58, external control 76.13+/-2.2organic As for exposed 80.87+/-1.46, internal control 83.05+/-1.49, external control 86.56+/-1.25Factors modulating biomarkers:GSTM1-null pol., P=0.024 in the exposedGSTT1-null pol., P=0.024, P=0.038in the external control. KEYWORDS CLASSIFICATION: analysis;Arsenic;Arsenicals;biomarkers of individual susceptibility: field studies;biomarkers of individual susceptibility: validation;Biotransformation;Cacodylic Acid;Case-Control Studies;Chile;Copper;genetics;Glutathione;Glutathione S-Transferase pi;Glutathione Transferase;Humans;metabolism;Male;Metallurgy;Middle Aged;Mining;Occupational Exposure;pharmacokinetics;Polymorphism,Genetic;Research;Spain;urine;field studies;genetic;blood.