A number of investigations (3-6) have been concerned with biochemical characteristics of nor-mal and leukemic leukocytes with special reference to enzymatic reactions that might represent po-tential targets for chemotherapeutic agents. Tetra-hydrofolate-dependent enzyme systems provide a particularly promising area for this approach, since they mediate reactions in which 1-carbon units are incorporated into precursors of nucleic acids and proteins, namely, inosinate, thymidylate, methionine, histidine, and serine (7-9). Further support for this reasoning is provided by other experimental facts: a) the levels of folic acid and folinic acid are considerably higher in acute leukemia cells than in normal cells (10); b) the folic acid antagonists (aminopterin, amethop-terin, and dichloroamethopterin) frequently pro-duce transient remissions in patients with acute leukemia; and c) the rate of incorporation of C14-formate and C14-formaldehyde into purines and into DNA-thymine is markedly increased in chronic myelocytic leukemic cells as compared with normal cells, and these processes are inhibited by aminopterin and amethopterin (11-13). In the present investigation several tetrahydro-folate-dependent enzymes and dihydrofolic re-ductase (14) have been studied in circulating hu-nman leukocytes. A comparison has been made of the level of these enzymes in normal cells and in *This work was supported by a grant (P-203) from the American Cancer Society. Preliminary reports of this work have appeared elsewhere (1, 2). tPostdoctoral fellow of the National Heart Institute.
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Bertino et al. (1963) studied this question.