Effects of beta-arabinofuranosyladenine on potentially lethal damage induced in plateau phase mammalian cells exposed to U.V.-light.

Abstract

The effect of beta-arabinofuranosyladenine (beta-araA), a specific inhibitor of DNA polymerases alpha and beta, on the survival of plateau phase Ehrlich ascites tumour cells (EAT-cells) after U.V.-exposure has been studied. beta-araA effectively inhibited repair of U.V.-induced potentially lethal damage (PLD), when given to the cells after irradiation. An exponential survival curve (D0 = 1 J/m2) was obtained when irradiated cells were treated with beta-araA at 120 microM. beta-araA mainly affected the shoulder width of the survival curve but also changed the slope of the resistant 'tail' of the survival curve. The effect of beta-araA on PLD was irreversible at 80 microM and only partly reversible at 20 microM. When beta-araA was added to cultures in either fresh or conditioned medium at 80 microM at various times after irradiation, there was a gradual decrease in the amount of PLD expressed. The survival reached levels corresponding to those of untreated cells plated immediately after irradiation. If cells were incubated for additional times in fresh medium, survival increased further to levels corresponding to those obtained with plateau phase cells after delayed plating. This further increase in survival did not occur in cells incubated in conditioned medium. The repair time constant for PLD was about 3 hours for cells incubated in fresh medium and about 6 hours for cells incubated in conditioned medium.