Base specificity in the inhibition of oncornavirus reverse transcriptase and cellular nucleic acid polymerases by antitumor drugs

Abstract

Adriamycin, daunomycin, acridylmethanesulfonanilide, and alkoxybenzophenanthridine alkaloids (coralyne acetosulfate, fagaronine chloride, and nitidine chloride) inhibit template-directed nucleic acid polymerizing enzyme activities like reverse transcriptase, DNA polymerase, and RNA polymerase. Enzyme reactions with poly(dA-dT), poly(rA)-oligo(dT) and poly(dA)-oligo(dT) are more strongly inhibited by the drugs than those with poly(dC)-poly(dG) and poly(rC)-oligo(dG). These results suggest that the antitumor drugs inhibit nucleic acid polymerases by a specific interaction with A:T base pairs of the templates.