Antitumor Activity of DL-ffà ̄reo-0-Fluoroasparagine against Human Leukemia Cells in Culture and L1210 Cells in DBA Mice1

DL-f/7reo-j8-Fluoroasparagine (DL-f/weo-/3-F-Asn) inhibited the growth of murine leukemia L1210 cells and three human leuke mia cell lines in culture. Fifty % inhibiting dose values ranged between 30 and 50 MMDL-fftreo-^-F-Asn. L1210 cells were not sensitive to DL-eryf/jro-/8-fluoroasparagine, DL-f/veo-/3-fluoroaspartic acid, or DL-e/yf/»ro-/3-fluoroaspartic acid at 300 MM, the highest dose studied. The antileukemia activity of DL-threo-ß-FAsn was studied in further detail using the L1210 model system. Inhibition of growth in culture was prevented by L-asparagine but not by o-asparagine. Inhibition of growth of L1210 cells incubated for 40 hr in the presence of 300 U.M DL-f/?reo-/3-F-Asn was reversed after DL-f/veo-/8-F-Asn removal. Treatment for longer periods of time resulted in cell lysis. DL-frireo-jS-F-Asn at doses of 250 mg/kg increased life span in mice bearing L1210 tumors by 60%. These results demonstrate the chemotherapeutic po tential of the amino acid analogue Di_-f/?reo-/î-F-Asn.