V. SPECIFICITY OF ACTION 147 



by others,^' ^'- ^" or by the same workers.*^ O'Dell and Hogan^' have stated 

 that xanthopterin is inactive in chicks fed on a (het low in P(1A. 



In vitamin M deficiency in the monkey, xanthopterin ha.s produced more 

 consistent effects. Totter and coworkers"- found that administration of 2.5 

 to U) mu;. of xantliopterin to vitamin M-deficient monkeys produced a 

 reticulocytosis in 3 to (> (hiys. 'I'lie white and red cell counts made transient 

 increases to normal levels in 3 to 13 days. Xanthopterin alone <i;iven i)ro- 

 l)hylactically failed to j^iotect completely but did delay the onset of nu- 

 tritional cytopenia. One animal given xanthopterin plus heated liver (shown 

 to be inefTective by itself) maintained a normal white and red cell count for 

 71 days. Removal of xanthopterin at this point resulted in prompt return 

 of cytopenia, and reinstatement of xanthopterin therapy produced a re- 

 sponse similar to the first. Cerecedo and his associates found that xanthop- 

 terin, like PGA, produced significant improvement in the lactation per- 

 formance of mice^-* and of rats."^ Definite but small hematologicid responses 

 have been noted by Heinle et al}'° in two PGA-deficient pigs given 10 mg. 

 of xanthopterin parenterally for 10 days. A third pig responded to a single 

 dose of xanthopterin.'*^ Cartwright et al." observed a reticulocyte response 

 of 9 % in one similarly deficient pig given a single injection of 20 mg. of 

 xanthopterin. 



The larva of the insect Ephestia kuehneola is able to utilize xanthopterin 

 in place of PGA but at levels one thousand times that of the vitamin."^ 



Another curious and still largely unexplained effect of xanthopterin was 

 noted early by Wright and Welch. ^^ When fresh rat liver is incubated with 

 xanthopterin a marked increase in the folic acid content of the preparation 

 is observed as compared with rat liver incubated either alone or with 

 leucopterin or certain purines or pyrimidines. In a more detailed investiga- 

 tion of this phenomena the same workers^^ found that the folic acid content 

 of rat liver and muscle was influenced during digestion by factors such as 



" L. D. Wright and A. D. Welch, Science 98, 179 (1943). 



*" X. E. .\xelrod, P. Gross, M. D. Bosse, and K. F. Swingle, ./. Biol. Chem. 148, 721 



(1943). 

 ^' B. L. O'Dell and A. G. Hogan, ./. Biol. Chem. 149, 323 (1943). 

 '•- J. R. Totter, C. F. Shukers, J. Kolson, V. Mims, and P. L. Day, /. Biol. Chem. 



152, 147 (1944). 

 " L. Mirone and L. R. Cerecedo, Arch. Biochem. 15, 324 (1947). 

 '' A. J. Sica, A. M. Allgeier, and L. R. Cerecedo, Arch. Biochem. 18, 119 (1948). 

 '^ R. W. Heinle, A. D. Welch, and H. L. Shorr, ./. Lah. Clin. Med. 34, 1763 (1949). 

 ^6 A. D. Welch and R. W. Heinle, Pharmacol. Revs. 3, 345 (1951). 

 " G. K. Cartwright, J. Fay, B. Tatting, and M. M. Wintrobe, /. Lab. Clin. Med. 33. 



397 (1948). 

 « G. Fraenkel and M. Blewett, Biochem. J. 41, 469 (1947). 

 ^9 L. D. Wright, H. R. Skeggs, and A. D. Welch, Arch. Biochem. 6, 15 (1945). 



