The effect of cyclocreatine on survival of CD2F1 mice implanted with the murine colon carcinoma C26 cells was investigated. The median survival of the control group (N=17) was 24 days, the mean 26 days compared to the CY-fed group (N=21), median 20 days, mean 21 days. The sole striking finding of the in vivo 31P spectra was the presence of considerable P-CY in the necrotic area which had insignificant amounts of ATP. 1H and 31P-NMR spectra were recorded of extracts of the tumors. The high content of -aminobutyric acid (GABA) was striking. There are no previous references to the presence of GABA in colon tumors in the literature although GABA uptake and localization has been demonstrated in nerve fibres and mucosal endocrine cells of the rat colon. If GABA content is greatly elevated in colon tumors, it may serve as a marker and be used to monitor treatment. We therefore have done some exploratory experiments to compare the GABA content in extracts of human colon tumors (2) and of adjoining normal colon tissue in the murine model C26. In both human and mouse colon tumors we found GABA values elevated 2-3 fold relative to normal colon tissue from the same source. Two colon cell lines, murine C26 and human Ht29 however, showed no elevation of GABA relative to other components of the extracts. These experiments will be repeated with a statiscally significant number of samples to determine the validity of these preliminary results. In addition, the HT29 human colon carcinoma cells will be implanted in nude mice to establish whether in vivo these cells will develop tumors with elevated GABA indicating the necessity of a host interaction.
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