Arsenite methylation by methylvitamin B-12 and glutathione does not require an enzyme

Although inorganic arsenic is methylated enzymatically by arsenic methyltra nsferases, which have been found in many mammalian livers, the detection of such enzymes has not been successful in surgically removed human livers. R esults of the present experiments demonstrated that methylvitamin B-12 (met hylcobalamin, CH3B12) in the presence of thiols and inorganic arsenite can produce, in vitro, substantial amounts of monomethylarsonic acid (MMA) and small amounts of dimethylarsinic acid (DMA) in the absence of enzymes, Furt hermore, this nonenzymatic methylation of inorganic arsenite by CH3B12 was increased substantially by the presence of dimercaptopropanesulfonate (DMPS ) and/or sodium selenite. The actions of DMPS and selenite together were ad ditive. The methylation by CH3B12 was neither inhibited nor stimulated by h uman liver cytosol, Since the amount of MMA produced by the in vitro system described in this study was not small, these results emphasize the need fo r a properly designed nutritional study in humans exposed to inorganic arse nic as to the relationship between vitamin B-12, selenium, and the metaboli sm of carcinogenic inorganic arsenic. (C) 1999 Academic Press.