Inhibition of purine metabolism in Ehrlich ascites carcinoma cells by phenanthridinium compounds related to ethidium bromide.

phenyl phenanthridinium bromide) has been shown to inhibit completely the incorporation of preformed purines into the nucleic acids of Ehrlich ascites carcinoma cells, but the drug does not ap preciably inhibit the incorporation of radioactive glycine into nucleic acids or proteins (4). These studies have been interpreted in terms of disrup tion of the normal relationship between intracellu lar pools of purine ribonucleotides synthesized from endogenously supplied purines or from purine ribonucleotides synthesized endogenously, al though the detailed mechanism remains obscure. A combination of ethidium bromide and azaserine, an agent which inhibits purine biosynthesis de novo (7), prolonged the survival time of mice given implants of Ehrlich ascites carcinoma by 400 per cent, and 50 per cent of the mice so treated were free of tumor at 50 days (5). Ethidium bromide has been shown not to be metabolized by mouse tissues and tumors and hence is itself the active inhibitor (6). A large number of phenanthridinium deriva tives have been synthesized and tested for their antitrypanosomal (1), antibacterial (8), and anti viral (3) activity. In the present study, ten phenanthridinium compounds in addition to ethid