Toxicity, disposition, and antitumor effects of L-canavanine in the rat
L-Canavanine, a nonprotein amino acid synthesized by higher plants, was only slightly toxic to rats following a single parenteral injection; the LD/sub 50/ was 6.77 +- 0.42 gkg in rats given a single sc injection. Pharmacokinetic evaluations indicated that canavanine was rapidly eliminated from the rat following a single dose; the systemic clearance value was 0.114 1hr and the T/sub 1/2 ..beta.. was 1.56 hr. Repeated sc administration of canavanine resulted in more severe toxicity. Histological studies of tissues from canavanine-treated rats revealed pancreatic acinar cell atrophy and fibrosis. Serum amylase and lipase were elevated after a single dose of canavanine; 3 or more daily injections resulted in a decrease in these digestive enzymes. The major metabolite recovered in the urine of rats that received a single 2.0 gkg dose of canavanine containing 5 ..mu..Ci L(guanidinooxy-/sup 14/C) canavanine was (/sup 14/C)urea. Significant amounts of (/sup 14/C) guanidine and respired /sup 14/CO/sub 2/ were also produced. Administration of 2.0 gkg canavanine daily for 5- or daily for 9-days produced significant inhibition of the growth of a solid rat colon tumor implanted subcutaneously. Increasing the dose to 3.0 gkgday resulted in regression of the tumor; however, cumulative toxicity, indicated by weight losses > 20%, was unacceptable at the higher dose
- Research Organization:
- Kentucky Univ., Lexington (USA)
- OSTI ID:
- 5335396
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
METABOLISM
TOXICITY
EXPERIMENTAL NEOPLASMS
GROWTH
CARBON 14 COMPOUNDS
INHIBITION
LARGE INTESTINE
RATS
SUBCUTANEOUS INJECTION
TRACER TECHNIQUES
ANIMALS
BODY
CARBOXYLIC ACIDS
DIGESTIVE SYSTEM
GASTROINTESTINAL TRACT
INJECTION
INTAKE
INTESTINES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
RODENTS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550901 - Pathology- Tracer Techniques