Mode of action of neocarzinostatin: Inhibition of DNA synthesis and degradation of DNA in Sarcina lutea

Abstract

Neocarzinostatin, a polypeptide anti-tumour substance produced by Streptomyces carzinostaticus, was investigated for its bactericidal action on Sarcina lutea. The primary action of the antibiotic on Sarcina lutea was the selective inhibition of DNA synthesis. Incorporation of [ 14C]thymidine into DNA was inhibited immediately after the addition of neocarzinostatin at a concentration as low as 0.005 μg/ml. Incorporation of [ 14C]uridine into RNA and of [ 14C]leucine into protein were not inhibited at a concentration of 0.5 μg/ml which caused almost complete inhibition of DNA synthesis. Moreover, DNA was markedly degraded into free bases at concentrations over 0.5 μg/ml. Despite the considerable DNA degradation, the DNA extracted from the cells treated with neocarzinostatin was able to serve as the template for DNA synthesis in vitro and did not differ from normal DNA in thermal denaturation profile. A relation between the mechanism of inhibition of DNA synthesis and degradation of DNA is discussed.