title: Micronucleus frequency in copper-mine workers exposed to arsenic is modulated by the AS3MT Met287Thr polymorphism.
abstract: Arsenic(III)methyltransferase (AS3MT) has been demonstrated to be the key enzyme in the metabolism of arsenic as it catalyses the methylation of arsenite and monomethylarsonic acid (MMA) to form methylated arsenic species, which have higher toxic and genotoxic potential than the parent compounds. The aim of this study is to evaluate if genetic variation in the AS3MT gene influences arsenic-induced cytogenetic damage, measured by the micronucleus (MN) assay. AS3MT Met287Thr allele frequencies and MN values were determined for 207 subjects working in the copper-mine industry, who were exposed to variable levels of arsenic. The urinary arsenic profile was used as individual biomarker of arsenic exposure. Results indicate that the MN frequencies found in peripheral blood lymphocytes of the exposed population poorly correlate with the levels of total arsenic content in urine. Nevertheless, when workers were classified according to their AS3MT Met287Thr genotypes, significantly higher MN values were observed for those carrying the variant allele [odds ratio (OR), 3.4 (1.6-5.2); P=0.0003)]. To our knowledge, these results are the first to show that genetic variation in AS3MT, especially the Met287Thr polymorphism, may play a role in modulating the levels of arsenic-induced cytogenetic damage among individuals chronically exposed to arsenic.
authors.affiliation: Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra, Spain; CIBER Epidemiología y Salud Pública, ISCIII, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Hernández
authors.affiliation: Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Leiliane
authors.initials: L
authors.lastname: Paiva
authors.affiliation: Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: Amadeu
authors.initials: A
authors.lastname: Creus
authors.affiliation: Departamento de Salud Ocupacional, División Codelco Norte, Corporación del Cobre de Chile, Chile.
authors.forename: Domingo
authors.initials: D
authors.lastname: Quinteros
authors.affiliation: Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra, Spain; CIBER Epidemiología y Salud Pública, ISCIII, Spain. Electronic address: ricard.marcos@uab.es.
authors.forename: Ricard
authors.initials: R
authors.lastname: Marcos
mesh_terms: D000328:Adult; D001151:Arsenic / Q000633:toxicity*; D003300:Copper; D006801:Humans; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D008875:Middle Aged; D008906:Mining; D020641:Polymorphism, Single Nucleotide
chemical_list: D003300:Copper; D008780:Methyltransferases; C505756:AS3MT protein, human; D001151:Arsenic
keywords: AS3MT; Arsenic; Cooper-mine workers; Met287Thr polymorphism; Micronucleus