Effects of adenosine deaminase inhibitor 2'-deoxycoformycin on the repair and expression of potentially lethal damage sensitive to β-araA

The effects of 2'deoxycoformycin, a specific inhibitor of adenosine deaminase, on the repair and fixation of potentially lethal damage (PLD) sensitive to treatment with β-araA, an adenosine analogue acting via inhibition of DNA polymerases α and β, have been studied. Given after irradiation deoxycoformycin alone had little effect on cell survival. More damage was nevertheless fixed by a given concentration of β-araA in the presence of deoxycoformycin to a degree that 35μM β-araA given simultaneously with 1 μg/ml deoxycoformycin produced the same effect (survival decrease to 20% of the controls) as 90 μM β-araA given alone. Maximum potentiation of the β-araA effect was observed atx1 μg/ml deoxycoformycin with a slight decrease at higher concentrations. Combined treatment with β-araA and deoxycoformycin reduced or eliminated the shoulder from the survival curve without affecting the slope, an effect similar to that observed after treatment of cells with β-araA alone. The results indicate the importance of adenosine deaminase in the inactivation of nucleoside analogues and are discussed vis-a-vis the possible practical application of this inhibitor in both experimental and therapeutic applications. (orig.)