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Effects of a Nitrogen Mustard on the Incorporation of Amino Acids into the Proteins of Tumor Slices¹

Department of Pediatrics, University of Miami School of Medicine, Miami, Florida

The effects of phenylalanine mustard on the incorporation of ³⁵S-labeled methionine into the proteins of tumor slices in vitro were studied in rats bearing the Walker 256 carcinosarcoma. Carcinostatic doses of phenylalanine mustard administered to the rat resulted in an inhibition of the incorporation of the amino acid into the protein of the tumor. The pattern of inhibition, in which effects on nuclear proteins were greater than those on cytoplasmic proteins, and its degree were virtually indistinguishable from those in which the incorporation study was carried out in vivo. On the other hand, when both the alkylating agent and the amino acid were administered in vitro, very high concentrations of the agent were required to produce inhibition, and the pattern differed in that effects on cytoplasmic proteins were prominent.

These data suggest the possibility that metabolic alterations in the agent are involved in its action in vivo and that the mechanisms under study when alkylating agents are employed in vitro may be different from those operating in vivo. They provide further evidence for the importance of the formation of nuclear proteins in the process of tumor growth.

¹ Aided by a grant from the Leukemia Society and Public Health Service Grant CA-08080 from the National Cancer Institute, NIH.

Received 9/30/65. Revised 1/ 3/66.