Methylation of Inorganic Arsenic in Different Mammalian Species and Population Groups
- 1 February 1999
- journal article
- research article
- Published by SAGE Publications in Science Progress
- Vol. 82 (1) , 69-88
- https://doi.org/10.1177/003685049908200104
Abstract
Thousands of people in different parts of the world are exposed to arsenic via drinking water or contaminated soil or food. The high general toxic of arsenic has been known for centuries, and research during the last decades has shown that arsenic is a potent human carcinogen. However, most experimental cancer studies have failed to demonstrate carcinogenicity in experimental animals, indicating marked variation in sensitivity towards arsenic toxicity between species. It has also been suggested that there is a variation in susceptibility among human individuals. One reason for such variability in toxic response may be variation in metabolism. Inorganic arsenic is methylated in humans as well as animals and micro-organisms, but there are considerable differences between species and individuals. In many, but not all, mammalian species, inorganic arsenic is methylated to methylarsonic acid (MMA) and dimethylarsinic acid (DMA), which are more rapidly excreted in urine than is the inorganic arsenic, especially the trivalent form (AsIII, arsenite) which is highly reactive with tissue components. Absorbed arsenate (AsV) is reduced to trivalent arsenic (AsIII) before the methyl groups are attached. It has been estimated that as much as 50–70% of absorbed AsV is rapidly reduced to AsIII, a reaction which seems to be common for most species. In most experimental animal species, DMA is the main metabolite excreted in urine. Compared to human subjects, very little MMA is produced. However, the rate of methylation varies considerably between species, and several species, e.g. the marmoset monkey and the chimpanzee have been shown not to methylate inorganic arsenic at all. In addition, the marmoset monkey accumulates arsenic in the liver. The rat, on the other hand, has an efficient methylation of arsenic but the formed DMA is to a large extent accumulated in the red blood cells. As a result, the rat shows a low rate of excretion of arsenic. In both human subjects and rodents exposed to DMA, about 5% of the dose is excreted in the urine as trimethylarsine oxide. It is obvious from studies on human volunteers exposed to specified doses of inorganic arsenic that the rate of excretion increases with the methylation efficiency, and there are large inter-individual variations in the methylation of arsenic. Recent studies on people exposed to arsenic via drinking water in northern Argentina have shown unusually low urinary excretion of MMA. Furthermore, children had a lower degree of methylation of arsenic than adults. Some studies indicate a lower degree of arsenic methylation in men than in women, especially during pregnancy. Whether the observed differences in methylation of arsenic are associated with variations in the susceptibility of arsenic remains to be investigated.Keywords
This publication has 112 references indexed in Scilit:
- Intake of Inorganic Arsenic in the North American DietHuman and Ecological Risk Assessment: An International Journal, 1998
- Dietary Arsenic Intake in Taiwanese Districts with Elevated Arsenic in Drinking WaterHuman and Ecological Risk Assessment: An International Journal, 1998
- Human HistamineN-Methyltransferase Gene: Structural Characterization and Chromosomal LocalizationBiochemical and Biophysical Research Communications, 1996
- Interactions of rat red blood cell sulfhydryls with arsenate and arseniteJournal of Toxicology and Environmental Health, 1995
- A chemical hypothesis for arsenic methylation in mammalsChemico-Biological Interactions, 1993
- Metabolism and excretion of orally and intraperitoneally administered trimethylarsine oxide in the hamsterToxicological & Environmental Chemistry, 1989
- The role of the methylation in the detoxication of arsenate in the rabbitChemico-Biological Interactions, 1985
- The effect of methyltransferase inhibition on the metabolism of [74As]arsenite in mice and rabbitsChemico-Biological Interactions, 1984
- Tissue distribution and retention of74As-dimethylarsinic acid in mice and ratsArchives of Environmental Contamination and Toxicology, 1984
- Intracellular interaction and metabolic fate of arsenite and arsenate in mice and rabbitsChemico-Biological Interactions, 1983