Antitumor Activity of dl-threo-β-Fluoroasparagine against Human Leukemia Cells in Culture and L1210 Cells in DBA Mice¹

dl-threo-β-Fluoroasparagine (dl-threo-β-F-Asn) inhibited the growth of murine leukemia L1210 cells and three human leukemia cell lines in culture. Fifty % inhibiting dose values ranged between 30 and 50 µm dl-threo-β-F-Asn. L1210 cells were not sensitive to dl-erythro-β-fluoroasparagine, dl-erythro-β-fluoroaspartic acid, or dl-erythro-β-fluoroaspartic acid at 300 µm, the highest dose studied. The antileukemia activity of dl-erythro-β-F-Asn was studied in further detail using the L1210 model system. Inhibition of growth in culture was prevented by l-asparagine but not by d-asparagine. Inhibition of growth of L1210 cells incubated for 40 hr in the presence of 300 µm dl-threo-β-F-Asn was reversed after dl-threo-β-F-Asn removal. Treatment for longer periods of time resulted in cell lysis. dl-threo-β-F-Asn at doses of 250 mg/kg increased life span in mice bearing L1210 tumors by 60%. These results demonstrate the chemotherapeutic potential of the amino acid analogue dl-threo-β-F-Asn.