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In vitro methylation of arsenite by rabbit liver cytosol: effect of metal ions, metal chelating agents, methyltransferase inhibitors and uremic toxins
- Source :
- Drug & Chemical Toxicology; 1999, Vol. 22 Issue 4, p613, 0p
- Publication Year :
- 1999
-
Abstract
- The methylation of carrier-free <superscript>74</superscript>As-arsenite by liver cytosol of Flemish Giant rabbits is highly susceptible to additions of trace elements. In vitro supplementation of essential trace elements like zinc (Zn<superscript>2+</superscript>), vanadium (V<superscript>5+</superscript>), iron (Fe<superscript>2+</superscript>), copper (Cu<superscript>2+</superscript>) and selenate was shown to increase the methylation efficiency. Trivalent metal ions (e.g. Al<superscript>3+</superscript>, Cr<superscript>3+</superscript> and Fe<superscript>3+</superscript>), Hg<superscript>2+</superscript>, Tl<superscript>+</superscript> and SeO3<superscript>2-</superscript> had a deleterious effect. The inhibitory effect of EDTA, oxime and many divalent cations (Ca<superscript>2+</superscript>, Mg<superscript>2+</superscript>, Sr<superscript>2+</superscript>, ...) suggest a co-factor role for a specific divalent metal ion, possibly Zn<superscript>2+</superscript>. Chelating agentsused in clinical treatment of acute and chronic inorganic arsenic poisoning lower the methylation capacity of cytosol by rendering the trivalent arsenic unavailable for the methyltransferase enzymes. S-adenosylhomocysteine and periodate-oxidized adenosine, inhibitors of s-adenosylmethionine dependent methylation pathways, inhibit the methylation of arsenite. Pyrogallol, a catechol-O-methyltransferase inhibitor, blocks the action of arsenite- and monomethylarsonic methyltransferase enzymes, suggesting a close structural relationship between the active sites of the different enzymes. Some uraemic toxins, namely oxalate, p-cresol, hypoxanthine, homocysteine and myo-inositol, inhibit arsenic methylation. [ABSTRACT FROM AUTHOR]
- Subjects :
- BIOCHEMISTRY
TOXICOLOGY
Subjects
Details
- Language :
- English
- ISSN :
- 01480545
- Volume :
- 22
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- Drug & Chemical Toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 8433522
- Full Text :
- https://doi.org/10.3109/01480549908993171