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SUMMARY: The action of 2:7-diamino-9-phenyl-10-ethyl phenanthridinium bromide (ethidium bromide) on the parasitic flagellate Strigomonas oncopelti has been studied. The drug is irreversibly active only against growing organisms. Addition of the drug to cultures of organisms in the logarithmic phase of growth did not result in an immediate inhibition of growth but in a progressive decrease in growth rate; at least a doubling in number of organisms always occurred before multiplication finally ceased. During the period of growth in the presence of drug the deoxyribonucleic acid content of the organisms fell to half its normal value whilst the ribonucleic acid remained approximately constant. Conditions have been determined which permit the synthesis of nucleic acids and proteins by washed suspensions of S. oncopelti and the effect of ethidium bromide on these processes has been studied. The drug rapidly inhibits DNA synthesis whereas RNA and protein synthesis continue for a period of 2–3 hr. after the addition of drug. A study has been made of the uptake of 14C-labelled ethidium bromide by organisms under conditions which will or which will not permit nucleic acid synthesis. The uptake of drug is of two types: (i) an initial rapid uptake which occurs in the absence of nucleic acid synthesis and which does not affect the subsequent growth of organisms; (ii) an additional uptake by growing organisms which appears to follow the course of RNA synthesis and which results, eventually, in an inhibition of growth.

The Mode of Action of Phenanthridines: The Effect of Ethidium Bromide on Cell Division and Nucleic Acid Synthesis