EFFECTS OF DOSE ON THE METHYLATION OF SELENIUM TO MONOMETHYLSELENOL AND TRIMETHYLSELENONIUM ION IN RATS

Mechanisms and metabolic significance in rats of methylation to the re duced form of selenium (Se), i.e., selenide (Se2-), were studied by do se- and time-related experiments with injection of selenite. Urinary S e-metabolites were determined by HPLC using an inductively coupled arg on plasma-mass spectrometer as an in-line detector (HPLC/ICP-MS method ). Although only monomethylselenol (MMSe) has been detected in urine o f normal rats even in those fed a Se-excess diet, the three types of S e-metabolites - MMSe, trimethylselenonium ion (TMSe), and inorganic Se , were detected in urine of Wistar rats injected with selenite (0, 0.1 , 0.3, 0.5 and 1.0 mg Se/kg body weight) into the tail vein. The amoun t of the three Se-metabolites was plotted against the total urinary Se concentration and shown to change dose- and time-dependently. The mon omethylated metabolite, i.e., MMSe, increased in urine rapidly at firs t and was slowly followed by linear dose-dependent ex cretion of the t rimethylated metabolite, TMSe. The new methylation pathway of MMSe lea ding to TMSe was assumed to be induced or activated when the dose of S e exceeds the limit of the normal capacity for monomethylation. Progre ssive methylation reactions were suggested to be regulated enzymatical ly.