Growth inhibition of a rat colon tumor by L-canavanine

The effects of L-canavanine, a higher plant nonprotein amino acid, on the growth of a rat colon carcinoma were assessed. The 1 and 10% lethal dose values following a single s.c. injection in Fischer rats were 4.75 and 5.57 g/kg, respectively. Rats received s.c. injections of a 10% (w/v) tumor cell suspension. When the tumors reached a size of 500 to 1000 mm3, the rats received canavanine, 2.0 g/kg or 3.0 g/kg s.c. daily for 5 or daily for 9 days. Control animals received a 0.9% NaCl solution. Administration of canavanine, 2.0 g/kg for 5 days produced a treated versus control of 23%; the treated versus control for 9 days was 14%. The 3.0-g/kg dosing regimen resulted in a treated versus control value of -13% after 5 days and -8% after 9 days. The negative values indicated regression of the tumor. The reduction in tumor volume, expressed as the percentage of regression, was 22% in animals receiving canavanine, 3.0 g/kg daily for 5 days and 60% in the 3.0-g/kg-daily-for-9-days treatment group. Cumulative toxicity caused death in 2 of 5 animals in the 3.0-g/kg-for-9-days treatment group; the average weight loss was 31%. The 3.0-g/kg-for-5-days treatment also produced undesirable cumulative toxicity as indicated by a weight loss of 19%. Cumulative toxicity was reduced greatly when canavanine was administered at a dose level of 2.0 g/kg for 5 days (weight loss of 13%). Analysis of the relationship of caloric deprivation to tumor growth reduction established that canavanine-mediated curtailment of tumor growth was not caused by reduced food intake and its associated loss in body weight. Histological examination of tissues from rats receiving canavanine, 2.0 or 3.0 g/kg daily for 5 or 9 days failed to reveal lesions in any of the examined tissues, except for varying degrees of pancreatic acinar atrophy. All other tissues appeared normal. The white and red blood cell values of canavanine-treated rats were also normal following 1, 3, or 6 injections of canavanine, 2.0 or 3.0 g/kg. The results indicated that canavanine induced marked growth inhibition of the rat colon carcinoma. Our experiments also disclosed that further studies must be conducted to optimize the dosing schedule to enhance drug efficacy and to reduce its cumulative toxicity.