Metabolic profile in workers occupationally exposed to arsenic: role of GST polymorphisms.
Arsenic 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.
Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Spain. ricard.marcos@uab.es
Ricardo
R
Marcos
Valeria
V
Martínez
Alba
A
Hernández
Amadeu
A
Creus
Chandra
C
Sekaran
Hiroshi
H
Tokunaga
Domingo
D
Quinteros
D001151:Arsenic / Q000493:pharmacokinetics* / Q000652:urine; D001152:Arsenicals / Q000652:urine; D001711:Biotransformation; D002101:Cacodylic Acid / Q000652:urine; D016022:Case-Control Studies; D002677:Chile; D003300:Copper; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008669:Metallurgy; D008875:Middle Aged; D008906:Mining; D016273:Occupational Exposure / Q000032:analysis*; D011110:Polymorphism, Genetic
D001151:Arsenic; D001152:Arsenicals; D002101:Cacodylic Acid; D003300:Copper; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human; C020300:monomethylarsonic acid