Methotrexate effects on hepatic betaine levels in choline-supplemented and choline-deficient rats.

Groups of rats fed both choline-supplemented and choline-deficient diets were injected with methotrexate (MTX) at dose levels of 0.1 mg/kg/day and 0.2 mg/kg/day. Both doses produced lowered hepatic betaine levels in the choline-supplemented animals when compared with nontreated, pair-fed controls. Since betaine levels were very low in the livers of choline-deficient rats, MTX had no further effect on hepatic betaine in these animals. These data suggest that the betaine lowering seen in livers of choline-fed rats may be due to utilization as a means of compensating for the MTX-induced loss of N5 methyltetrahydrofolate for the vital methylation of homocysteine in methionine biosynthesis.