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( Biomedical Division, The Samuel Roberts Noble Foundation, Inc., Ardmore, Oklahoma)
Previous studies with canavanine led to the present testing of the effects of canaline and other compounds related to arginine, ornithine, and citrulline on Jensen sarcoma cell cultures. Canaline inhibited proliferation of the tumor cells in vitro by 50 per cent at 0.1 mM concentration. The inhibition was not competitive with ornithine, but it was prevented by pyridoxal phosphate and glutamic acid semialdehyde. The toxicity of canaline probably rested, therefore, in "carbonyl-trapping" properties of its substituted hydroxylamine structure.
In related studies, the
-hydroxy and
-keto analogs of arginine could neither inhibit proliferation nor support it in the absence of arginine. Two lower and one higher (homoarginine) homologs of arginine were similarly ineffective, as were a number of other related compounds. Two lower homologs each of citrulline and ornithine and one higher (homocitrulline) of citrulline could not inhibit cellular proliferation appreciably.
In contrast to the above results with arginine analogs and homologs, several arginine-containing peptides and protamines not only could supplant arginine in the culture medium but also markedly stimulated proliferation. L-Prolyl-L-phenylalanyl-L-arginine and two protamines, clupeine and salmine, most stimulated proliferation, producing ca. 50 per cent more new cells than in control culture with free arginine. L-Valyl-L-arginine and L-prolyl-L-arginine supported proliferation but did not stimulate it appreciably. L-ß-Methylaspartyl-L-arginine supported proliferation but did not inhibit it. D-Alanyl-L-arginine could only partially spare the arginine requirement, while L-phenylalanyl-L-citrulline was incapable of replacing arginine.
* Portions of this study were presented at meetings of the Southwest Section, Am. Assoc. for Cancer Research, Oklahoma City, November, 1961, and the Tissue Culture Assoc., Washington, D.C., May, 1962.
Received 3/ 6/63.
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