Lack of Methylation of Inorganic Arsenic in the Chimpanzee

Vahter, Marie; Couch, Ronald C.; Nermell, Barbro; Nilsson, Robert

doi:10.1006/taap.1995.1150

Cited by 91 publications

(55 citation statements)

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“…Recently, Aposhian (1996) suggested that wide-ranging As-methylating capabilities of mammals might be due to a genetic polymorphism of the methyltransferase enzymes, induced by environmental characteristics, such as the presence of high amounts of inorganic arsenic in the food and water supply and the occurrence of sleeping sickness. The lack of methylation of arsenic in the chimpanzee shown by Vahter et al (1995a) and the striking differences in the ratio of arsenic metabolites observed by Vahter et al (1995b) in urine between native Andean women exposed to high arsenic levels in drinking water and other humans can be interpreted in the same manner.…”

Section: Discussionmentioning

confidence: 91%

Basal Metabolism of Intraperitoneally Injected Carrier-Free ⁷⁴As-Labeled Arsenate in Rabbits

et al. 1996

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74As]arsenate metabolites in Flemish Giant rabbits was investigated. As absorbed rapidly, reaching maximal concentrations in plasma and packed cells after 30 min and 2 hr, respectively. As species is lower than that in other rabbits and more similar to that of humans. The tissue 74 As distribution varied widely with the highest concentrations in kidneys, liver, and lungs. 74As accumulated in bone whereas other tissues and blood showed rapid clearance rates. In muscle and heart an important part of arsenic was associated with components insoluble in phosphate-buffered isotonic saline. Binding of arsenic to soluble tissue proteins was most important in the kidneys, liver, and spleen. [ The biotransformation of arsenic in humans and other mammals is dependent on the chemical form administered. Arsenate and arsenite are methylated in vivo initially into monomethylarsonic acid (MMA) and subsequently to dimethylarsenic acid (DMA) (Tarn et al., 1979a;Yamauchi and Yamamura, 1983). This methylation process can be seen

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Section: Discussionmentioning

confidence: 91%

Basal Metabolism of Intraperitoneally Injected Carrier-Free ⁷⁴As-Labeled Arsenate in Rabbits

et al. 1996

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“…We compared the AS3MT genotypes in human (H. sapiens), rat (R. norwegicus), and mouse (M. musculus) which methylate iAs with the AS3MT genotype of chimpanzee (P. troglodytes), a species that lacks the capacity to methylate iAs (Aposhian, 1997;Vahter et al, 1995). The AS3MT cDNA sequences (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Of these, three (rat, mouse, human) are known to be efficient methylators of iAs. In contrast, the chimpanzee has been shown to lack the capacity to methylate iAs (Aposhian, 1997;Vahter et al, 1995). This examination of AS3MT at the genomic and proteomic levels suggests a molecular basis for this interspecies difference in iAs methylation phenotype.…”

Section: Introductionmentioning

confidence: 85%

Arsenic (+3 oxidation state) methyltransferase and the inorganic arsenic methylation phenotype

Waters

Drobná

et al. 2005

Toxicology and Applied Pharmacology

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Inorganic arsenic is enzymatically methylated; hence, its ingestion results in exposure to the parent compound and various methylated arsenicals. Both experimental and epidemiological evidences suggest that some of the adverse health effects associated with chronic exposure to inorganic arsenic may be mediated by these methylated metabolites. If iAs methylation is an activation process, then the phenotype for inorganic arsenic methylation may determine risk associated with exposure to this metalloid. We examined inorganic arsenic methylation phenotypes and arsenic (+3 oxidation state) methyltransferase genotypes in four species: three that methylate inorganic arsenic (human (Homo sapiens), rat (Rattus norwegicus), and mouse (Mus musculus)) and one that does not methylate inorganic arsenic (chimpanzee, Pan troglodytes). The predicted protein products from arsenic (+3 oxidation state) methyltransferase are similar in size for rat (369 amino acid residues), mouse (376 residues), and human (375 residues). By comparison, a 275-nucleotide deletion beginning at nucleotide 612 in the chimpanzee gene sequence causes a frameshift that leads to a nonsense mutation for a premature stop codon after amino acid 205. The null phenotype for inorganic arsenic methylation in the chimpanzee is likely due to the deletion in the gene for arsenic (+3 oxidation state) methyltransferase that yields an inactive truncated protein. This lineage-specific loss of function caused by the deletion event must have occurred in the Pan lineage after Homo-Pan divergence about 5 million years ago. D

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“…Along with the EA and IA groups, we sequenced both hNP and hGSTO1-1 in one chimpanzee DNA sample (data not shown). Chimpanzees, the closest nonextinct primate relative of humans, do not biotransform arsenic into methylated species but do demonstrate arsenate reductase activity (Vahter et al 1995;Wildfang et al 2001). Thus, it was not surprising that we observed a high degree of protein homology between humans and chimpanzees in hNP and hGSTO1-1, with only one amino acid difference between human and chimpanzee hGSTO1-1, a conservative substitution of isoleucine (human) for valine (chimp) at residue 26.…”

Section: Discussionmentioning

confidence: 99%

Genetic variation in genes associated with arsenic metabolism: glutathione S-transferase omega 1-1 and purine nucleoside phosphorylase polymorphisms in European and indigenous Americans.

Li¹,

Kalla²,

Guthrie³

et al. 2003

Environ Health Perspect

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Individual variability in human arsenic metabolism has been reported frequently in the literature. This variability could be an underlying determinant of individual susceptibility to arsenicinduced disease in humans. Recent analysis revealing familial aggregation of arsenic metabolic profiles suggests that genetic factors could underlie interindividual variation in arsenic metabolism. We screened two genes responsible for arsenic metabolism, human purine nucleoside phosphorylase (hNP), which functions as an arsenate reductase converting arsenate to arsenite, and human glutathione S-transferase omega 1-1 (hGSTO1-1), which functions as a monomethylarsonic acid (MMA) reductase, converting MMA(V) to MMA(III), to develop a comprehensive catalog of commonly occurring genetic polymorphisms in these genes. This catalog was generated by DNA sequencing of 22 individuals of European ancestry (EA) and 24 individuals of indigenous American (IA) ancestry. In hNP, 48 polymorphic sites were observed, including 6 that occurred in exons, of which 1 was nonsynonymous (G51S). One intronic polymorphism occurred in a known enhancer region. In hGSTO1-1, 33 polymorphisms were observed. Six polymorphisms occurred in exons, of which 4 were nonsynonymous. In contrast to hNP, in which the IA group was more polymorphic than the EA group, in hGSTO1-1 the EA group was more polymorphic than the IA group, which had only 1 polymorphism with a frequency > 10%. Populations representing genetic admixture between the EA and IA groups, such as Mexican Hispanics, could vary in the extent of polymorphism in these genes based upon the extent of admixture. These data provide a framework in which to conduct genetic association studies of these two genes in relevant populations, thereby allowing hNP and hGSTO1-1 to be evaluated as potential susceptibility genes in human arsenicism.

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Lack of Methylation of Inorganic Arsenic in the Chimpanzee

Cited by 91 publications

References 0 publications

Basal Metabolism of Intraperitoneally Injected Carrier-Free ⁷⁴As-Labeled Arsenate in Rabbits

Basal Metabolism of Intraperitoneally Injected Carrier-Free ⁷⁴As-Labeled Arsenate in Rabbits

Arsenic (+3 oxidation state) methyltransferase and the inorganic arsenic methylation phenotype

Genetic variation in genes associated with arsenic metabolism: glutathione S-transferase omega 1-1 and purine nucleoside phosphorylase polymorphisms in European and indigenous Americans.

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Lack of Methylation of Inorganic Arsenic in the Chimpanzee

Cited by 91 publications

References 0 publications

Basal Metabolism of Intraperitoneally Injected Carrier-Free 74As-Labeled Arsenate in Rabbits

Basal Metabolism of Intraperitoneally Injected Carrier-Free 74As-Labeled Arsenate in Rabbits

Arsenic (+3 oxidation state) methyltransferase and the inorganic arsenic methylation phenotype

Genetic variation in genes associated with arsenic metabolism: glutathione S-transferase omega 1-1 and purine nucleoside phosphorylase polymorphisms in European and indigenous Americans.

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Product

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Basal Metabolism of Intraperitoneally Injected Carrier-Free ⁷⁴As-Labeled Arsenate in Rabbits

Basal Metabolism of Intraperitoneally Injected Carrier-Free ⁷⁴As-Labeled Arsenate in Rabbits