Aminopterin and A-methopterin, well known folic acid antagonists, have been shown to inhibit the incorporation of C14 from formate into nucleic acids and nucleic acid purines. Under the conditions of these experiments, incorporation of C14O2 into purines was partially blocked, but no decrease was observed in tissue CO2 fixation. The relationship of these observations to the mechanism of action of folic acid in purine synthesis and the anti-leukemic mechanism of “folic acid inhibitors” is discussed.

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This work was supported by the American Cancer Society, upon recommendation of the Committee on Growth of the National Research Council; the Research Fund of the Southern Research Institute; and Mr. Ben May, Mobile, Alabama. Certain data reported herein were obtained in a program supported by the Atomic Energy Commission, Division of Biology and Medicine. The authors wish to acknowledge the technical assistance of Mrs. Constance Nolan, Miss Linda Simpson, Miss Margaret Ann Newton, Miss Martelia Bell, and Mrs. Janita Chapman.

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