Amethopterin and liver purine metabolism in vivo.

Amethopterin in toxic amounts, whether given in a single dose or in repeated daily doses, produced no observable inhibition of the nicotinamide-induced synthesis of diphosphopyridine nucleotide in mouse liver in vivo. Likewise, no inhibition was de tected of the incorporation of formate-C14 into the total liver acid-soluble adenine. However, administration of amethopterin sufficient to produce loss in body weight brought about a progressive increase of as much as 30-fold in the specific activity of the acid-soluble adenine of the liver, after injection of formate-C14, glycine-1-C14, or glycine-2-C14. Increased labeling, correlated with amethopterin toxicity, was obtained