THERAPEUTIC EFFECTS OF D-ASPARTIC ACID BETA-HYDROXAMATE (DAH) ON FRIEND-ERYTHROLEUKEMIA

D-aspartic acid beta-hydroxamate (DAH), an aspartic acid analogue, exe rts anti-tumoral activity against murine leukemia L5178Y both in vitro and in vivo. We show here that DAH displays activity against Friend l eukemia cells (FLC) in vitro: a concentration of 2 mM results in a tot al inhibition of cell growth. DAH is also active in vivo against Frien d virus (FV-P)-induced erythroleukemia. Treatment with DAH, given for 95 days as a single daily i.p. injection to DBA/2 mice 3 days followin g FV-P inoculation, induced a marked increase of 212% in the mean surv ival time (MST) of treated animals. Since FV-P-induced erythroleukemia is characterized by the proliferation of mature erythroid precursors, we examined the effect of DAH treatment on erythroid colony-forming c ells (CFU-E) and observed that the number of CFU-E per spleen was 30 t imes lower in DAH-treated mice than in the controls. To gain further i nsight into the early effects of DAH treatment on the early phase of F riend disease, we examined the effects of short DAH treatment on splee n size, hematocrit and viremia in FV-P-infected mice. DAH treatment in itiated 3 days post infection (p.i.) inhibited splenomegaly, prevented virus-induced polycythemia, and reduced serum viremia. Late DAH treat ment (18 days p.i.) induced regression of FVP-induced disease as evide nced by reduction of spleen weight. (C) 1994 Wiley-Liss, Inc.