Antitumor activity of L-canavanine against L1210 murine leukemia

We have made a preliminary assessment of the antitumor activity of the arginine analog, L-canavanine, 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 x DBA/2 F mice bearing L1210 leukemic cells. Following an i.v. injection of 10 mg canavanine, the t1/2 beta of canavanine in the serum was estimated at 16 min. This finding suggested that frequent injections of high doses of canavanine 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/hr for 24 hr caused an 86% inhibition of DNA synthesis. The antitumor activity of canavanine was tested against L1210, using a 24-hr infusion schedule with treatment starting 24 hr after i.p. inoculation of 10(5) cells. An optimal dose of 18 g/kg body weight produced a median increased lifespan of 44% (p less than 0.005). These results suggest that L-canavanine may be useful as an antitumor agent.