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

The effect of β-arabinofuranosyladenine (β-araA), a specific inhibitor of DNA polymerases α and β, on the survival of plateau phase Ehrlich ascites tumour cells after U.V.-exposure has been studied. β-araA 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 β-araA at 120 μM. β-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 was irreversible at 80 μM and partly reversible at 20 μM. When β-araA was added to cultures in fresh or conditioned medium at 80 μM at various times after irradiation, there was a gradual decrease in PLD. 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 to levels corresponding to those obtained with plateau phase cells after delayed plating, but 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 incubated in conditioned medium. (author)