Effects of nitrogen mustards on the incorporation of amino acids into the proteins of tumors and other tissues; the mustard derivative of serine

The effects of O-[N-di-(2-chloroethyl)carbamoyl]-dl-serine, a nitrogen mustard derivative of serine, on the incorporation of amino acids into proteins have been studied in rats bearing the Walker 256 carcinosarcoma. The intraperitoneal injection of 1,500 mg of the compound/kg regularly induced carcinostasis and occasionally produced complete regression of the tumor, while producing minimal systemic toxicity. These effects were accompanied by an inhibition of the incorporation of amino acids into the protein of the tumor. The degree of inhibition was always greater in the nuclear proteins than in the cytoplasmic proteins, suggesting a predominantly antinuclear action which is consistent with biologic information about alkylating agents. It is proposed that these findings are related to the mechanism of action of these compounds. The inhibition observed after administration of serine mustard occurred only in the tumor, while other mustards such as HN2 and uracil mustard have been shown to inhibit these processes in a variety of nontumor tissues. Serine mustard was as effective in the inhibition of the formation of proteins from methionine as from serine. These data suggest that the compound acts not as an analogue inhibitor but as an alkylating agent with altered tissue specificity.