Effects of β-Arabinofuranosyladenine on the Growth and Repair of Potentially Lethal Damage in Ehrlich Ascites Tumor Cells

Abstract

.beta.-D-Arabinofuranosyladenine (.beta.-araA) inhibits the growth of [mouse] Ehrlich ascites tumor cells by selective inhibition of DNA synthesis via DNA polymerases. RNA and protein synthesis are not significantly affected. Addition of .beta.-araA to the cells after irradiation resulted in a concentration-dependent decrease in survival, presumably due to the inhibition of the repair of potentially lethal damage. Since .beta.-araA selectively inhibits DNA polymerases, repair of potentially lethal damage probably involves steps at the DNA level which require some polymerization. These repair steps take place in the DNA with a velocity comparable to that of the repair of potentially lethal damage. The inhibition of the repair of potentially lethal damage by .beta.-araA was modified by the addition of deoxyadenosine; .beta.-araA probably acts competitively against dATP at the molecular level. The inhibition of the repair of potentially lethal damage by .beta.-araA, which is partly reversible, resulted in a concentration-dependent modification of the survival curve. At low concentrations of .beta.-araA a dose-modifying decrease in survival was observed. At higher concentrations (more than 12 .mu.M) the decrease in survival resulted in a decrease of the shoulder width of the survival curve. Eventually an exponential curve was obtained. The shoulder of the survival curve probably results from some repair of potentially lethal damage. Preliminary information was obtained on the time course of this repair.