V. SPECIFICITY OF ACTION 159 



voruin factor is also otlVc'tixc in con iil era di 1112; the toxicity of l-ainiiio IMIA 

 lor the o«!;i2; cinhryo.'''' 



Tclrahtji>u)ia (jclcii is uuiciue ainoii>j; the P(iA-ie(iuiring organisms in 

 that it is not inhibited by either 4-amino PGA or N'^-methyl PGA. It has 

 been reported that 4-amino PGA functions as a growth piomoter, but this 

 was later shown to be due to appi-eciable amounts of PGA which were 

 present in the sample of 4-amino PGA (Heinrieh et al.^^). Although N^"- 

 methyl PGA functions as a growth promoter and 4-amino PGA neither 

 stimulates nor inhibits growth, 4-amino- 10-methyl PGA, as well as 4-amino- 

 9-methyl PGA, functions as an antagonist (Dewey et al.'"). 



The resistance of T. geleii to 4-amino PGA is similar to that of a strain 

 of >S. faecalis R which had become resistant to 4-amino- 10-methyl PGA by 

 repeated culture in the presence of this antagonist (Burchenal et al.^^). 

 Broquist et al.^^ has found that the resistance of this organism to 4-amino 

 PGA is due to an increased ability to convert PGA to the citrovorum fac- 

 tor. 



8. Effect of Antagonists on Experimental Tumors 



The striking effect of PGA in stimulating growth of white cells in PGA- 

 deficient animals provided a basis for the suggestion that PGA antagonists 

 might be able to reduce the large number of white cell blood elements 

 which form in leukemia. Clinical w^ork has borne out the validity of the 

 assumption.""' and a large amount of data has accumulated on the effects 

 of these antagonists in experimentally induced tumors of various types. 

 Interesting in this connection is the observation that the PGA and citro- 

 vorum factor content of leucocytes is higher in leukemia than in normal 

 blood. In advanced stages of the disease, leucocytes may contain as high 

 as 300 m7 of citrovorum factor per milliliter as compared with normal 

 levels of 30 to 80 my per milliliter (Swendseid et a/.""). 



The growth of Rous chicken sarcoma, which is a virus disease and thus 

 not necessarily directly related to other types of tumors, is inhibited by a 

 PGA deficiency. The deficiency can be induced either by feeding a diet 



35 W. W. Cravens and E. E. Snell, Proc. Soc. Exptl. Biol. Med. 75, 43 (1950). 



'« M. R. Heinrieh, V. C. Dewey and G. W. Kidder, /. Am. Chem. Soc. 75, 5425 (1953). 



9" V. C. Dewey, G. W. Kidder, and R. E. Parks, Jr., Proc. Soc. Exptl. Biol. Med. 78, 



91 (1951). 

 58 J. H. Burchenal, G. K. Waring, and D. J. Hutchison, Proc. Soc. Exptl. Biol. Med. 



78, 311 (1951). 

 " H. P. Broqui.st, \. R. Kohlcr, D. .i. Hutchison, and J. H. Burchenal, ./. Biol. Chem. 



202, 59 (1953). 

 lo" S. Farber, Blood 7, 97 (1952). 

 '<" M. E. Swendseid, F. H. Bethell, O. D. Bird, Cancer Research 11, S64 (1951). 



