Reversal of Aphidicolin-Directed Inhibition of DNA Synthesis in vivo and in vitro by Deoxyribonucleosides or Their 5'-Triphosphates

Abstract

The inhibitory effects of aphidicolin on growth and DNA synthesis in vivo in mouse [mammary carcinoma] FM3A cells were reversed by the simultaneous addition of all 4 deoxyribonucleosides to the culture. In lysolecithin-permeabilized FM3A cells the inhibition of DNA synthesis by aphidicolin was reversed by increasing the concentrations of all 4 dNTP, but not by increasing the concentrations of 3 of the 4. DNA synthesis in permeabilized cells exhibited a close resemblance to that in vivo with respect to its sensitivity to aphidicolin and its type of inhibition. A 100-fold higher concentration of aphidicolin was required to inhibit DNA polymerase .alpha. and its inhibition was reversed only by dCTP.