Effects of adenosine deaminase inhibitor 2'-deoxycoformycin on the repair and expression of potentially lethal damage sensitive to beta-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 beta-araA, an adenosine analogue acting via inhibition of DNA polymerases alpha and beta, have been studied. Given after irradiation deoxycoformycin alone had little effect on cell survival. More damage was nevertheless fixed by a given concentration of beta-araA in the presence of deoxycoformycin to a degree that 35 microM beta-araA given simultaneously with 1 microgram/ml deoxycoformycin produced the same effect (survival decrease to 20% of the controls) as 90 microM beta-araA given alone. Maximum potentiation of the beta-araA effect was observed at 1 microgram/ml deoxycoformycin with a slight decrease at higher concentrations. Combined treatment with beta-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 beta-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.