US EPA

1251704 

Journal Article 

The effect of dietary and chemically induced methylation deficiency on the metabolism of arsenate in the rabbit 

Marafante, E; Vahter, M 

1986 

Yes 

Acta Pharmacologica et Toxicologica
ISSN: 0001-6683 

NIOSH/00166634 

59 Suppl 7 

35-38 

English 

3776588 

WOS:A1986E682400005 

Effects of a low dietary intake of choline (62497) on the biosynthesis of dimethylarsinic-acid (75605) (DMA) and on the tissue retention of arsenic (7440382) (As) were studied in New-Zealand-white-rabbits exposed to arsenate (7778394). Rabbits were given a choline deficient diet or a standard diet containing 600mg/kg choline for 10 weeks. One hour before administration of labeled As, animals in one of the standard diet groups were given an intraperitoneal injection of 100 micromoles/kilogram periodate-oxidized adenosine (PAD). Labeled arsenate was injected into the external ear vein. Inhibition of methyltransferase activity by injection of PAD resulted in a marked decrease in the production of As-DMA following exposure to labeled AsV. Rabbits given PAD excreted only about 50 percent as much labeled As-DMA as did the rabbits given labeled As only. Thus, they retained a significantly higher percentage of labeled As in the liver, lungs, and skin. In rabbits given a choline deficient diet, there was a similar decrease in urinary excretion of labeled As-DMA, and an increased retention of labeled As in the tissues. These effects were probably caused by interaction of unmethylated As with tissue constituents. Choline deprivation gave rise to an increased concentration of labeled As in the liver microsomes, whereas PAD treatment did not. The authors conclude that nutritional factors, as well as agents interacting with transmethylase activity in the liver, may be important for the toxic response following exposure to inorganic As. 

DCN-153350; Dietary effects; Laboratory animals; Poisons; Metabolites; Enzyme activity; Tissue distribution; Liver microsomes