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 killingy by 5FT. These results support the hypothesis that cell death occurs due to malfunctioning proteins which contain 5FT residues.
D000818:Animals; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D014176:Protein Biosynthesis; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D014364:Tryptophan