Effects of 2'-deoxycoformycin infusion on mouse adenosine deaminase.

low concentrations it appears to be relatively specific for ADase, although other sites of action with a lower affinity for DCF have been reported (3, i 5). Indeed, the cytotoxicity of ara-A (6, 25) and 3'-deoxyadenosine (20, 24) is notably en hanced by DCF, and this compound also potentiates the ara-A therapy of mice bearing Li 210 leukemia (26). Previous studies in our laboratory (33) indicate that in re sponse to in vivo administration of the tight-binding but revers ible inhibitor erythro-9-(2-hydroxy-3-nonyl)adenmne, ADase 1ev els are elevated in certain tissues. These data suggest potential mechanisms of enzyme induction or derepression that must be considered in any attempt to use ADase inhibitors in vivo. The present study documents a tissue-dependent effect of contin uous infusion of DCF on mouse ADase and purine nucleoside phosphoryiase levels and compares these data to the response in vitro. A significant conclusion of these studies is that inhibition of ADase after infusion of DCF is not complete but that its extent is tissue dependent. Indeed, the enzyme in vivo appears to be much less sensitive to inhibition than in vitro data predict. We have also documented that the presence of a transplantable tumor can have dramatic influences on the response to DCF. These data may be useful in understanding the clinical re sponse to ADase inhibitors, as weli as in elucidating mecha nisms of enzyme regulation in general.