ANTI-TUMOR ACTIVITY OF L-CANAVANINE AGAINST L1210 MURINE LEUKEMIA

  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (3) , 535-537
Abstract
The antitumor activity of the arginine analog, L-canavanine, was studied in leukemic mice. This analog is known to substitute for arginine in protein biosynthesis in many prokaryotic and eukaryotic systems. Previous studies with cells grown in vitro indicated that canavanine caused a marked inhibition of DNA synthesis and viability. The system used in the present study was C57BL/6 .times. DBA/2 F1 mice bearing L1210 leukemic cells. Following an i.v. injection of 10 mg canavanine, the t1/2.beta. [elimination half-life] of canavanine in the serum was estimated at 16 min. Frequent injections of high doses of canavanine probably would be required for an effect on tumor cell proliferation. DNA synthesis by the L1210 cells, assayed by [3H]thymidine incorporation, fell to 9% of the control value after 12 hourly i.p. injections of canavanine (20 mg each). A constant s.c. infusion of 20 mg/h for 24 h caused an 86% inhibition of DNA synthesis. The antitumor activity of canavanine was tested against L1210, using a 24 h infusion schedule with treatment starting 24 h after i.p. inoculation of 105 cells. An optimal dose of 18 g/kg body weight produced a median increased lifespan of 44% (P < 0.005). L-Canavanine may be useful as an antitumor agent.

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