Observations on the action of azaserine in mammalian tissues.

Azaserine has been shown to be an inhibitor of de novo purine synthesis (4, 8). In studies with mice bearing ascites cell tumors, inhibition of purine synthesis was shown to correlate with in creased survival time of the hosts (7). It was fur ther demonstrated that the significant effect of the drug on the tumor cells involved a reaction between azaserine and a constituent of the cells (3, 7). This reaction was irreversible in that the drug could not be washed away and that a single dose inhibited de novo purine synthesis for ap proximately 12 hours. Reaction between the drug and the cells took only 8-10 minutes of direct con tact. This type of study has now been extended to experiments with solid tumors growing subcutaneously. This drug is unable to completely inhibit tu mor growth because it blocks only one of two pathways of purine nucleotide synthesis, both of which are available to all experimental neoplasms that we have tested (6). The incorporation of pre formed adenine into nucleic acids was not in hibited by azaserine (2). Treated tumor cells can, therefore, continue to synthesize nucleic acids, which are essential for their further growth and multiplication. Azaserine also produces deleterious side effects in humans, which complicate its use as a chemotherapeutic agent (1). In view of the na ture of action of this drug, which appears to be a "titration" of an enzyme in the tumor cells, the