The metabolism of tritiated thioacetamide in the rat

Abstract

Abstract A method is described for preparing tritiated thioacetamide. Thioacetamide‐ 3 H was fed daily to rats at a level which is known to produce liver tumours after six months' feeding. It was shown that less than 1% was excreted unchanged in the urine. Radioactivity was found in all the organs examined and in the chemical constituents of all cell fractions of the liver suggesting metabolism of thioacetamide to acetate. Measurements of the acetate pool size and of the quantity of thioacetamide entering the pool showed that over 95% of the carcinogenic dose of thioacetamide was converted to acetate in 24 hr. Following incubation of thioacetamide with liver slices it was shown that the pathway of metabolism is through acetamide. Liver slices were seen to be three times more active than kidney slices in converting thioacetamide to acetamide and it is suggested that this metabolic step is a necessary prerequisite to the toxic and carcinogenic effects of thioacetamide in the liver.