The most outstanding feature of pederine is undoubtedlyits potency: concentrations of the orderof 1.5 ng/ml, corresponding to 3 X 10- 9 M, aresufficient to cause cellular death within 4 days inall the cell lines analyzed, and an immediate impairmentof protein and DNA synthesis; thisamount of drug corresponds to a maximum ofapproximately 107 molecules available per cell, ifone assumes that the cultures concentrate immediatelyall the drug within the cells. Pederine is,therefore, from 1,000 to 10,000 times more activethan the most common antimetabolites. The cytologicalobservations on the effect of pederine areof little help for the study of the specificity ofaction of the compound: in fact, all the cell alterationsobserved are suggestive of a generalized cytopathogeniceffect. The analysis of macromolecularsyntheses seems to yield more information.The block of protein synthesis seems to takeplace immediately, i.e. within 10 min after theaddition of the drug, and, therefore, much earlierthan any appreciable morphological alterations;the block of DNA replication is nearly simultaneouswith that of protein synthesis, but is perhapsof a slightly less degree. This little difference(Fig. 2), and the earlier recovery of amino acidincorporation after removal of the drug (Fig. 5),indicate that protein synthesis is affected first; thisconclusion is strengthened by the apparent
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