Elucidating the pathway for arsenic methylation

Rated 4.59/5 based on 544 customer reviews

Analyses of these standards yielded recoveries between 80 and 109%. Anonymous DNA samples from healthy individuals of self-reported ancestry were obtained from the Coriell Institute (Camden, NJ, USA).

We studied 22 samples from individuals of European ancestry (EA), and 24 samples from individuals of indigenous American ancestry (IA).

The detection limits, quality control, precision, and accuracy of this analytical method were assessed. Genetic variation in genes associated with arsenic metabolism: glutathione S-transferase omega 1-1 and purine nucleoside phosphorylase polymorphisms in European and indigenous Americans. Zakharyan RA, Sampayo-Reyes A, Healy SM, Tsaprailis G, Board PG, Liebler DC, et al. Human monomethyl-arsenic acid (MMA(V)) reductase is a member of the glutathione-S-transferase superfamily. Maria Mercedes Meza, (1), * Lizhi Yu, (2), * Yelitza Y.

The detection limits were 0.42-1.08 [micro]g/L for arsenic compounds. Rodriguez, (2) Mischa Guild, (2) David Thompson, (2) A. Klimecki (2)(1) Department of Natural Resources, Sonora Institute of Technology (ITSON), Ciudad Obregon, Sonora, Mexico; (2) Arizona Respiratory Center, and (3) Department of Pharmacology and Toxicology, University of Arizona, Tucson, Arizona, USAAddress correspondence to W. Klimecki, Arizona Respiratory Center, University of Arizona, P.

The accumulated samples were then shipped on dry ice to the University of Arizona, where the samples were stored at -80[degrees]C until the analysis was performed. Urine samples were digested with nitric acid using a microwave oven, following published protocols (Francesconi et al. Freeze-dried urine reference material for trace elements (Clinchek-control; RECIPE, Munich, Germany), containing arsenic at a level of 68 [micro]g As/L, was used for quality control and to validate the assay. E-mail: [email protected] arc.arizona.edu* These authors contributed equally to the manuscript.

Accuracy values were calculated by spiking standard compounds of all the species that were studied [10 [micro]g/L As(III), As(V), and MMA(V); 20 [micro]g/L DMA(V)] in urine samples. Similar recovery experiments used reference urine samples (Institut National de Santee Publique Quebec, Quebec, Canada), containing As(III), MMA(V), and DMA(V). All subjects were in good health (self-reported and by physical examination) and free from any skin lesions suggestive of arsenic toxicity.Although we did not track the characteristics of individuals who declined to be in the study, participation rate was estimated to be 90% of the individuals who attended the informational meetings.Initial phenotypes evaluated included the ratio of urinary inorganic arsenic(III) to inorganic arsenic(V) and the ratio of urinary dimethylarsenic(V) to monomethylarsenic(V) (D: M). GSTO is capable of the reduction of monomethylarsenic(V) [MMA(V)] to monomethylarsenic(III) (Nemeti and Gregus 2004).In the initial association screening, three polymorphic sites in the CYT19 gene were significantly associated with D: M ratios in the total population. More recently, the case for genetic determinants of variability in human arsenic metabolism was strengthened by Chung et al. (Recently the HUGO-recognized name for CYT19 has been designated AS3MT.) Some but not all reports show that PNP is capable of functioning in the reduction of arsenate to arsenite (Nemeti et al. CYT19 was initially characterized as an arsenic methyltransferase in rodents that is capable of the methylation of inorganic arsenic to its monomethyl form, and of monomethylarsenic to its dimethylarsenic form (Lin et al. In rodents, CYT19, in the presence of the proper system of reducing equivalents, has been proposed to be capable of the entire gamut of arsenic biotransformations that begin with arsenite and end with dimethylarsenic(V) [DMA(V)] (Thomas et al. These studies have provided the identity of candidate genes and the basis for beginning the genetic association studies necessary to test the hypotheses of the existence of genetic determinants of interindividual variability of arsenic metabolism. In addition, catalogs of polymorphic sites in PNP have been published for European and indigenous Americans (Yu et al. Despite the availability of these catalogs, only one genetic association study has been reported (Marnell et al. To address the need for genetic association studies aimed at testing the hypothesis of the existence of genetic determinants of interindividual variability in human arsenic metabolism, we used existing polymorphism catalogs for GSTO and PNP, produced a resequencing-derived catalog of polymorphisms in CYT19 (no such resequencing-based catalog was publicly available), and tested 23 polymorphic sites within these three genes in a population of arsenic-exposed subjects from the Yaqui Valley area of Sonora, Mexico, who had been phenotyped for the levels of urinary metabolites of arsenic.

Leave a Reply