Therapeutic effects of D-aspartic acid beta-hydroxamate (DAH) on Friend erythroleukemia.
D-aspartic acid beta-hydroxamate (DAH), an aspartic acid analogue, exerts anti-tumoral activity against murine leukemia L5178Y both in vitro and in vivo. We show here that DAH displays activity against Friend leukemia cells (FLC) in vitro: a concentration of 2 mM results in a total inhibition of cell growth. DAH is also active in vivo against Friend 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 following FV-P inoculation, induced a marked increase of 212% in the mean survival 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 cells (CFU-E) and observed that the number of CFU-E per spleen was 30 times lower in DAH-treated mice than in the controls. To gain further insight into the early effects of DAH treatment on the early phase of Friend disease, we examined the effects of short DAH treatment on spleen size, hematocrit and viremia in FV-P-infected mice. DAH treatment initiated 3 days post infection (p.i.) inhibited splenomegaly, prevented virus-induced polycythemia, and reduced serum viremia. Late DAH treatment (18 days p.i.) induced regression of FVP-induced disease as evidenced by reduction of spleen weight.
Tournaire
R
R
INSERM U.218-Centre Léon Bérard, Lyon, France.
Malley
S
S
Hamedi-Sangsari
F
F
Thomasset
N
N
Grange
J
J
Dore
J F
JF
Vila
J
J
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001216:Asparagine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D005622:Friend murine leukemia virus; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy* / Q000382:microbiology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D011086:Polycythemia / Q000188:drug therapy; D012192:Retroviridae Infections / Q000188:drug therapy*; D013163:Splenomegaly / Q000188:drug therapy; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014412:Tumor Virus Infections / Q000188:drug therapy*; D014766:Viremia / Q000188:drug therapy
D000998:Antiviral Agents; C024848:beta-aspartylhydroxamic acid; D001216:Asparagine