Effects of Tryptophan Mustard on Incorporation of Amino Acids Into Proteins In Tumor-Bearing Rats2

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Abstract
The effects of 5-[bis(2-chloroethyl)amino]-DL-tryptophan, a nitrogen mustard derivative of tryptophan, on the incorporation of amino acids into proteins have been studied in rats bearing the Walker 256 carcinosarcoma. The intravenous injection of 0.8 mg per kg of the mustard regularly induced carcinostasis and occasionally produced complete regression of the tumor. These effects were accompanied by an inhibition of the incorporation of amino acids into the proteins of the tumor. The degree of inhibition was always greater in the nuclear than in the cytoplasmic proteins, which confirmed a predominantly antinuclear action observed with other alkylating agents. The inhibition of amino acid incorporation, which followed the administration of tryptophan mustard occurred only in the tumor, while nonamino acid mustards such as nitrogen mustard (HN2) and uracil mustard had suppressive effects on the uptake of amino acids into the proteins of a number of nontumor tissues. The spleen decreased in size, but the incorporation of tryptophan into proteins of the spleen was markedly increased after treatment with tryptophan mustard. Tryptophan mustard was equally effective in the inhibition of the formation of tumor proteins from tryptophan and arginine. These data suggest that this amino acid mustard does not act as an analogue inhibitor but as an alkylating agent with altered tissue specificity.

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