118 HAROLD KOEMG 



adenine into RNA in vivo is depressed by FO (Fig. 12). FO evidently inter- 

 feres with the biosynthesis of RNA in neural tissue. The mechanism by which 

 FO brings about a depletion of RNA, however, has not been ascertained at 

 the time of this writing. 



The well-known participation of RNA in protein synthesis has led us to 

 investigate the uptake of labeled amino acids into protein. Initially, FO does 

 not depress the incorporation of tagged methionine and lysine into neural 

 protein. A depression of 50-85% is observed after 1 week, however. Signifi- 

 cantly, the greatest depression in uptake is observed in cases of severe neu- 

 ronopathy, i.e., when areflexic paraplegia is present. Thus, a loss of neuronal 

 function is associated with a greater depletion of RNA and a severe defect 

 in protein biosynthesis in afTected nerve cells (Fig. 13). The formation of 

 spurious RNA molecules also could contribute to the defect in protein 

 synthesis. 



The role of pyrimidine nucleotides as cofactors in lipid and polysaccharide 

 biosynthesis and in interconversion of sugars has been recognized recently 

 (Henderson and LePage, 1958). The formation of spurious fluoropyrimidine 

 nucleotides suggests that disturbances in lipid and carbohydrate metabolism 

 may be partly responsible for the neurologic disorders that are produced by 

 the fluorinated pyrimidines. This possibility is being investigated. The bio- 

 chemical basis for the neuronal hyperirritability also remains to be elucidated. 



If- 



■4 



Fig. 12. Autoradiographs showing depressed uptake of orotic-6-C" into RNA of 

 lumbar motoneuron 2 days after FO. Control on left, experimental on right. X 700. 



