CHEMICAL INTERFERENCE WITH PHAGE GROWTH 281 



well as tail pins (Kellenberger and Sechaud, 1957). Thus the 

 synthesis of at least four macromolecular phage components 

 proceeds unhampered by proflavine. Phage production is 

 arrested at a late stage that may call for the assembly of these 

 several components (Chapter XI). 



The mechanism by which proflavine interferes with matura- 

 tion is unknown. It may act directly on an enzyme required for 

 assembly, or block the synthesis of an unknown phage constitu- 

 ent, or alter the nucleic acid produced. Nucleic acids are 

 known to combine chemically with the acridines and the often 

 reported ability of nucleic acids, both RNA and DNA, to reverse 

 the inhibitory action of acridines may well be an expression of 

 this chemical combination. An indication that the DNA 

 formed by phage-infected bacteria under proflavine inhibition 

 may be diff'erent from normal phage DNA was described by 

 Astrachan and Volkin (1957). DNA labeled with P^^ ^^s 

 isolated from the proflavine-treated system and mixed with 20 

 times the amount of authentic phage DNA. The nucleotide 

 sequences obtained by degradation of the DNA mixture were 

 then examined for differences in specific activities. Differences 

 could not be detected among the products which were obtained 

 by the action of deoxyribonuclease. However, significant 

 differences were found at higher levels of organization among 

 the larger polynucleotide fragments obtained by heating the 

 DNA mixture. 



Final ex'aluation of the mechanism of action of proflavine must 

 also take into account the reports of Manson (1954, 1957) 

 describing inhibitory effects on DNA synthesis. In a medium 

 containing a low level of inorganic phosphate sufficient for 

 normal growth of T2, proflavine prevents the synthesis of DNA 

 and utilization of glucose and inorganic phosphate. With 

 a high level of phosphate, phage development is still suppressed 

 but DNA synthesis is normal. In T5 infection, high levels of 

 phosphate do not suffice to reverse proflavine inhibition of DNA 

 synthesis. 



