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The Effects of DL-p-Fluorophenylalanine and L-3-Nitrotyrosine on the Growth and Biochemistry of the Taper Liver Tumor¹

Department of Chemistry, University of Calgary, Calgary 44, Alberta, Canada

Two amino acid analogs, DL-p-fluorophenylalanine and L-3-nitrotyrosine, retarded the growth of Taper liver tumor in mice and increased mouse survival time. Both of the analogs were taken into the tumor cells in vitro and in vivo, and DL-p-fluorophenylalanine inhibited the uptake of L-phenylalanine in vitro.

tRNA in the "pH 5 fraction" from tumor cells could be acylated with DL-p-fluorophenylalanine-¹⁴C, and DL-p-fluorophenylalanine-¹⁴C was incorporated into protein of tumor cells in vivo. DL-p-Fluorophenylalanine also caused inhibition of L-phenylalanine tRNA formation.

Pyrophosphate formation could not be detected after incubation of L-3-nitrotyrosine with the pH 5.0 fraction from tumor cells, and there was no evidence of L-3-nitrotyrosine incorporation into tumor protein in vivo. Very high concentrations of L-3-nitrotyrosine were required to inhibit L-tyrosine tRNA formation in vitro.

The studies, therefore, showed that there was a relationship between the biochemical effects of DL-p-fluorophenylalanine and its retardation of growth, while this relationship did not seem quite as significant with L-3-nitrotyrosine.

¹ This research was supported in part by National Research Council of Canada Grant A-4691.

Received 3/ 1/71. Accepted 7/ 6/71.

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