Green M H, Brooks T L, Mendelsohn J, Howell S B
Cancer Res. 1980 Mar;40(3):535-7.
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.
我们已经对精氨酸类似物L-刀豆氨酸在白血病小鼠中的抗肿瘤活性进行了初步评估。已知这种类似物在许多原核和真核系统的蛋白质生物合成中可替代精氨酸。先前对体外培养细胞的研究表明，刀豆氨酸会显著抑制DNA合成和细胞活力。本研究使用的系统是携带L1210白血病细胞的C57BL/6×DBA/2 F小鼠。静脉注射10 mg刀豆氨酸后，血清中刀豆氨酸的t1/2β估计为16分钟。这一发现表明，要对肿瘤细胞增殖产生影响，需要频繁注射高剂量的刀豆氨酸。通过[3H]胸腺嘧啶掺入法测定，L1210细胞的DNA合成在每12小时腹腔注射刀豆氨酸（每次20 mg）后降至对照值的9%。以20 mg/hr的恒定皮下输注速率持续24小时，导致DNA合成受到86%的抑制。使用24小时输注方案，在腹腔接种10(5)个细胞后24小时开始治疗，测试刀豆氨酸对L1210的抗肿瘤活性。最佳剂量为18 g/kg体重，可使中位生存期延长44%（p<0.005）。这些结果表明，L-刀豆氨酸可能作为一种抗肿瘤药物有用。
