Enzymologyof Pyrimidineand Carbohydrate Metabolism in HumanColon Carcinomas

The purpose of this study was to elucidate the biochemistry of human primary colon tumors and to relate the relevance of the enzymology of chemically induced, transplantable mouse tumors and human colon carcinoma xenografts to that of the human primary colon tumor. The enzymology of pyrimidine, carbohydrate, pentose phosphate, and galactose metabolism of 14 cases of primary colon tumors was comparedwith that of colon mucosa from the same patients. There was a marked alteration in the enzymology of the human colon tumor that distinguished it from that of the normal mucosa. In pyrimidine metabolism,there was an increase in the specific activities of the enzymes of both de novo biosynthesis [carbamoyl-phos phate synthetase II, cytidine 5'-triphosphate synthetase,oroti dine 5'-monophosphatedecarboxylase,and aspartatecarbam oyltransferase (3.2-, 3.1-, 1.7-, and 3.2-fold)] and of those of the salvage pathway [deoxycytidine kinase, thymidine kinase, and uridine-cytidine kinase (4.6-, 3.0-, and 2.2-fold)]. By con trast, the activity of the catabolic enzyme, uridine phosphoryl ase, decreasedto 64%. There was a trend toward an increase in activities of enzymesof glycolysis and of pentosephosphate production. Galactokinase activity was increased 4-fold. The most stringent linkage of enzyme activities in human colon neoplasia was observed for those increased in 100% of the examined cases (galactokinase, deoxycytidine kinase, car bamoyl-phosphatesynthetase II, aspartate carbamoyltransfer ase, and cytidine 5'-triphosphate synthetase). A comparisonof the humanprimary colon tumors and of the experimental model systems revealed both similar and con trasting enzymic patterns. In pyrimidine metabolismof mouse tumors, the alterations were similar or more pronounced than those in humancolon carcinomas;this was consistent with the higher growth rate of mouse tumors. The activities of the pentose phosphate enzymes in the mouse tumor were not elevated as compared to activities of the normal mousecolon mucosa, whereas in the human tumors the activities were increased above those of human normal colon mucosa. The enzymic profile of the slowly growing humancarcinoma xeno graft was similar to that of the normal human colon mucosa. The well-defined enzymic alterations of the human primary colon tumors were in betweenthose of the slow and the rapidly growing xenografts, forming a gradient towards the profound biochemical imbalanceof the rapidly growing colon carcinoma xenograft.