Abstract
The biochemical effects on Ehrlich ascites cells of acriflavine, podophyllotoxin, 6-hydroxylaminopurine, and 8-ethoxycaffeine, compounds known to inhibit cell multiplication, were studied. Acriflavine was shown to inhibit DNA synthesis, and extracts of cells preincubated with acriflavine were less able to synthesize inosinate. Podophyllotoxin was a potent inliibitor of purine synthesis in vitro but relatively ineffective in vivo. It did block purine interconversion, and the general inhibitory effects of the agent were attributed to this action. The adenine analog, 6-hydroxylaminopurine, blocked the conversion of inosinate to adenylate and guanylate. This specific inhibition led to a generalized decrease in formation of nucleic acids. Purine synthesis de novo was blocked by 8-ethoxycaffeine in extracts of ascites cells, the effect was much greater when the cells had been preincubated with the inhibitor. The action of this compound was attributed to this specific block. The compounds each appeared to have distinct modes of action. It is suggested that some of these may mimic natural mechanisms of control of cell division.
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