TOXICOLOGIC STUDIES OF ANTITUMOR AMINO ACID DERIVATIVES IN MICE AND RATS

抄録

Toxicity of five antitumor amino acid derivatives, N-β-naphthalenesulfonyl-DL-tryptophan(A-91), β-naphthylaminomethyl-γ-aminobutyric acid (A-144), N-ethylcarbaminomethyl-L-isoleucine(A-145), N-9-fluorenylacetyl-Lphenylalanine(A-192), and N-propionyl-L-valine(A-195) were studied in mice and rats. These amino acid derivatives (A-A derivatives), with the exception of A-192, were less toxic in mice and rats administered single intraperitoneally (ip) and orally(po).
In repeated-dose studies with the five A-A derivatives, the rats were treated ip with daily doses of one-third LD50 every day for 10 days. During the observation period, the rats treated with A-A derivatives, with the exception of A-195, showed no adverse signs and caused no body weight loss. However, some rats treated with A-195 developed poor apetite or anorexia, weight loss, and death during the two weeks observation period. Treatment of A-A derivatives caused no leukopenia, as in treatment of Mitomycin-C, and the other hematologic toxicity was slightly changed compared with the control groups.
Renal and hepatic functions were slightly affected in rats treated with A-A derivatives.
Severe lesions were noted in testes of rats treated with Mitomycin-C, but treatment with A-A derivatives caused moderate lesions in testes. All other tissues appeared to be normal.
These results indicate that the toxicity of A-A derivatives is less toxic than that of Mitomycin-C in animals.