Reversal of Aminopterin Inhibition in the Chick Embyro with Desoxyribosides. ∗

Abstract

Summary

Aminopterin, injected prior to, or early in, the incubation period, is highly toxic to the chick embryo. Ten micrograms or more of this compound produce 100% mortality; 100 μg or more per egg completely inhibit embryonic development. The inhibitor becomes relatively less toxic as embryonic development progresses; at nine days or more, twenty micrograms is non-toxic. The same amount injected at three days results in almost immediate embryonic death.

Thymidine partially counteracted the inhibitory effects of aminopterin. A combination of hypoxanthine desoxyriboside and thymidine was more effective than thymidine alone. In the absence of thymidine, hypoxanthine desoxyriboside was without effect. An enzymatic digest of desoxyribonucleic acid also counteracted aminopterin inhibition partially. Thymine, hypoxanthine, folic acid, vitamin B₁₂, and concentrates of the Leuconostoc citrovorum factor, alone and in various combinations, were ineffective in counteracting aminopterin inhibition.

These experiments indicate that aminopterin acts in animal tissues in part by preventing synthesis of thymidine and one or more of the purine desoxyribosides, and that these compounds are immediately essential for embryonic growth. Since aminopterin is thought to act by creating a deficiency in folic acid, the necessity for folic acid in synthesis of these compounds in animal tissues is implied.