Actinomycin and antitumor antibiotics.

Abstract

Actinomycin D forms a stable complex with DNA and thereby inhibits theDNA-dependentsynthesisof RNA. The biochemical effectsof this antibiotic upon cells in culture are interpretable in terms of the complex described above. They include inhibition of the synthesis of ribosomal RNA at low drug concentrations, of all RNA species at moderate concentrations and of both RNA and DNA at very high concentrations. Given in adequate quantity, actinomycin D will inhibit synthesis of RNA in intact animals; the effect seen in a given tissue will depend upon the drug concentration achieved therein. Cytotoxicity is seen primarily in proliferating cells; it correlates better with prolonged tissue retention of the drug than with an acute inhibitory effect upon RNA metabolism. The factors responsible for selective retention of the drug within a tissue remain to be determined. Other antibiotics which may be grouped by chemical structure as anthracyclines and chromomycins also form stable complexes with DNA and inhibit synthesis of RNA.