The mechanism of killing of mouse fibroblasts by the amino acid analogue 5‐fluorotryptophan

The mechanism of killing of A9 fibroblasts by 5‐fluorotryptophan has been studied. L‐tryptophan competitively relieves the growth inhibition caused by 5FT. After incubation with 5FT, ³H‐5FT was incorporated into protein, replacing tryptophan residues. During the initial hours of incubation with 5FT, a specific inhibition was observed of the incorporation of L‐tryptophan into protein; later this inhibition was followed by a general inhibition of protein synthesis and cell division. However, nuclear division continued after cell division had ceased. While 5FT was observed to be incorporated into protein after a 1 hour period in MEM + 0.40 mM 5FT in A9, no ³H‐5FT was incorporated into protein in a mutant isolated by its resistance to killing by 5FT. These results support the hypothesis that cell death occurs due to malfunctioning proteins which contain 5FT residues.