Aphidicolin and deoxycoformycin cause DNA breaks and cell death in unstimulated human lymphocytes

Human lymphocytes lose viability when incubated in vitro with either aphidicolin, an inhibitor of DNA polymerase alpha, or with the combination of aphidicolin and deoxycoformycin (an adenosine deaminase inhibitor). Loss of viability was assayed by vital staining with fluorescein diacetate as well as examination of Wright stained preparations and the appearance of cellular debris observed using an electronic cell counter. The loss of viability was rapid with the combination of aphidicolin (2 micrograms/ml) and deoxycoformycin (1 microgram/ml) with essentially complete loss of viability after 72 hours of incubation. This drug combination produces DNA single strand breaks after 24 and 48 hours of incubation at a level equivalent to that produced by 200 or 400R of X-irradiation, respectively.