Levels of dihydrofolate reductase and the formate-activating enzyme activities in guinea pig tissues before and after amethopterin administration

Abstract

Formate-activating enzyme activity and dihydrofolate reductase activity have been measured in the tissues of the guinea pig; the highest levels of these enzyme activities occur in the liver and kidney. After the administration of amethopterin, the liver and kidney retained this drug for at least 14 days, while bone marrow, small intestine, and spleen contained amounts not detectable by bioassay methods (less than 1 × 10 −7 μmoles/mg protein in lysates). Dihydrofolate reductase activity in liver, kidney, spleen, bone marrow, and small intestine did not increase after amethopterin administration (5 mg/kg body weight given subcutaneously); however, a two- to four-fold increase was observed in circulating erythrocytes 7 to 21 days after the administration of the drug. Dietary deficiency of folate did not produce significant changes in the dihydrofolate reductase activity of liver, bone marrow, erythrocytes, or leukocytes of guinea pigs. The erythrocytes and leukocytes of various animal species have measurable levels of dihydrofolate reductase activity, except the erythrocytes of the dog and the red and white cells of man.