NUCLEIC ACID ANTIMETABOLITES AND CNS 



117 



PUMP 

 ♦•PCDP 



FCMP 



70 



FUDP 

 +FCTP 



POMP 

 i FUDPAG 

 .FUDPG 



FUTP 



100 150 200 



Tube No. 



2 50 



300 



Fig. 11. Chromatogram of acid-soluble fraction of spinal cord obtained by extended 

 gradient elution with formic acid-ammonium formate from Dowe.x 1 column. Tissue 

 removed 4 hours after the intraspinal injection of FO-2-C". 



Key: — D 260 um: Radioactivity of C". 



of FU and FC probably accounts for failure of these analogs to produce 

 neurologic distiubances. Similar anabolic conversions of these fluorinated 

 pyrimidines ha\e been described in other organs i Harbers ct al., 1959). 



The morphologic distribution of incorporated FO has been e.xamined by 

 high resolution autoradiography ( Koenig and Young. 1960). FO is taken up 

 into RNA of neurons and oligodendroglia and leptomeningeal. ependymal, 

 and Schwann cells. Initially FO is incorporated into nuclear RNA. Some 

 labeling of cytoplasmic RNA is discerned in nerve cells after a day or so; 

 however, FO persists in nuclear RNA for a number of weeks. 



Metabolic Effects of FO 



The histopathologic changes produced by FO suggest a depletion of 

 neuronal RNA. The results of biochemical analysis corroborate this inference 

 (Koenig ct ai, 1960a) . The concentration of RNA in gray and white matter 

 of spinal cord diminishes by 30-50% after 1 week. A greater depression in 

 RNA concentration occurs in animals with areflexic paraplegia than in those 

 with hyperactive reflexes. The incorporation of labeled orotic acid and 



