Studies on the folic acid vitamins.V. The effect of folic acid on the citrovorum factor activity of mouse liver

OLIC ACID administered to mice 1 hour be-F fore a lethal dose of aminopterin prevents death due to the drug.8A nonlethal "priming" dose (LD,) of aminopterin abolishes this protective effect.'Simultaneous administration of folinic acid (5-formyl-5,6,7,8-tetrahydropteroylglutamic acid) also protects from aminopterin toxicity, but this protection is not abolished by a prior dose of aminopterin.789It was concluded from these data that aminopterin interferes with the in vivo metabolic conversion of folic acid to a material with citrovorum factor (CF) activity,Q as previously shown by Nichol and Welch in vitro.12The further demonstration by Nicholll that the administration of folic acid was followed by an increase in the citrovorum factor activity of rat liver supported this idea.In connection with investigations of the mechanism of action of the folic acid antagonists, a study was undertaken to determine whether these drugs could be shown to interfere with this augmentation of hepatic citrovorum factor activity.We felt this approach might offer another method for assay of dose response relationships with these drugs. METHODS Materials.The mice used were (BALB/ cAnxDBA/2J)F1 hybrid males about 3 months