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.