Effect of phenylalanine on the toxicity of 4-fluorophenylalanine for the rat.

The acute toxicity of 3-fluorotyrosine and of 3-fluorophenylalanine for animals was reported several years ago (2) and recently it was found that 2and 4-fluorophenylalanines likewise are toxic when administered to albino rats (3). 3-Fluorotyrosine and 3-fluorophenylalanine are very efficient in acting as antimetabolites for tyrosine and phenylalanine, respectively (4), while 4-fluorophenylalanine inhibits the growth of microorganisms (5). In spite of the fact that tyrosine and phenylalanine were able to overcome in a competitive manner the inhibition of growth of microorganisms caused by 3-fluorotyrosine and 3-fluorophenylalanine, it did not seem reasonable to expect that the great toxicity’ of these derivatives to animals receiving an adequate diet could be due to their action as antimetabolites for their parent amino acids. The purpose of the present investigation was to examine the effect of phenylalanine in counteracting the toxicity of 4-fluorophenylalanine for the rat. This study was of considerable interest because only a few of the many known competitive antagonists for amino acids, ethionine (6-9), methoxinine (lo), and p-2and P-3-thienylalanines (ll-13), have been studied to determine whether their toxic effects to animals can be removed by the presence of an excess of the parent amino acids. In the case of the thienylalanines the workers concluded that the toxicities could be removed completely by the addition of an excess of the normal metabolite to the diet. With ethionine and methoxinine, however, there is strong evidence to indicate that factors other than a simple competitive antagonistic action towards methionine are responsible for their toxicity to animals.