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Inorganic arsenic methylation by rat tissue slices
B Georis1, A Cardenas, J P Buchet
1Unité de Toxicologie Industrielle et de Médecine du Travail, Catholic University of Louvain, Bruxelles, Belgium.
Toxicology
|July 1, 1990
Summary
Rat liver, kidney, and lung tissues methylate trivalent inorganic arsenic (AsIII). The liver exhibits the highest methylating capacity, influenced by reduced glutathione, which facilitates AsIII metabolism and dimethylarsinic acid (DMA) excretion.
Area of Science:
- Biochemistry
- Toxicology
- Cell Biology
Background:
- Trivalent inorganic arsenic (AsIII) is a toxic metalloid.
- Arsenic metabolism and methylation are critical detoxification pathways.
- Understanding arsenic methylation in different organs is crucial for toxicology.
Purpose of the Study:
- To investigate the methylation capacity of rat liver, kidney, and lung tissues for AsIII.
- To elucidate the role of reduced glutathione (GSH) in arsenic metabolism.
- To examine the effects of AsIII excess and mercuric ions on arsenic methylation.
Main Methods:
- Incubation of rat liver, kidney, and lung slices with AsIII.
- Measurement of monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) production.
- Assessment of AsIII uptake and intracellular binding in liver cells.
- Evaluation of GSH's role and the impact of mercuric ions on methylation.
Main Results:
- Liver, kidney, and lung slices methylate AsIII to MMA and DMA, with the liver showing the highest capacity.
- AsIII enters liver cells via diffusion, binds extensively intracellularly, and is regulated by GSH.
- GSH facilitates AsIII diffusion, stimulates methylation, and enhances DMA excretion; excess AsIII reversibly inhibits DMA production.
- Mercuric ions inhibit MMA and DMA production by reducing As uptake and methylation; MMA can be methylated to DMA in liver slices, stimulated by GSH.
- Pentavalent arsenic (AsV) is poorly methylated due to limited hepatocyte uptake.
Conclusions:
- The liver is the primary organ for arsenic methylation in rats, with GSH playing a key regulatory role.
- Arsenic methylation is a complex process influenced by substrate concentration, cofactors like GSH, and inhibitory ions.
- Differential uptake and methylation of AsIII and AsV highlight distinct metabolic fates and toxicological implications.