[PRODUCTION OF CLONES OF MOUSE ASCITES SARCOMA 37].
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The relatively broad and overlapping specificities of amino acid transport systems have made the synthesis of analogues specific to single transport systems desirable. The analogue in general use as a specific substrate for transport system L has been 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid (BCH). The affinity of BCH for the binding site of system L has been shown to be less than that of the natural substrate, leucine. Earlier studies from this laboratory suggested that higher homologues in a series could have greater affinity for system L. A higher homologue of BCH, 2-aminobicyclo[3.2.1]octane-2-carboxylic acid (ABOCA), has been synthesized and studied as a substrate and competitor for amino acid transport systems of the sarcoma 37 (S37) ascites cell. ABOCA inhibited the transport system dominant in the low concentration region for histidine uptake (system L) but had no effect on the uptake of labeled N-methyl-alpha-aminoisobutyric acid (MeAIB). MeAIB had no effect on labeled ABOCA uptake in S37 cells. ABOCA inhibited the uptakes of labeled leucine and labeled BCH competitively. Leucine, histidine, and BCH inhibited the uptake of labeled ABOCA competitively. Typical L system substrates demonstrated exchange effects with labeled ABOCA. The b isomer of ABOCA demonstrated slightly greater affinity for system L than did the a isomer. We conclude that ABOCA is an analogue restricted to interaction with amino acid transport system L, that it has greater affinity for system L than does BCH, and that its selection for system l is determined principally by an apolar interaction with steric considerations secondary.
Treatment with such analgetics as analginum, promedol and pantopon was shown experimentally either to inhibit or to stimulate the growth of sarcoma-37 and its dissemination. It was also found to reduce the tumor growth--stimulating effect of operative trauma.
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The inoculation of sarcoma-37 against the background of the ganglionary blockade, provided by the intraperitoneal injection of 1 ml of pentamine, is not associated with its less take rate, but there is a manifest suppression of the tumor growth during the period up to 63 days. A preliminary ganglionary blockade completely eliminates the stimulating effect of a trauma on the tumor growth.
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