SUBSTRATE BALANCES ACROSS COLONIC CARCINOMAS IN HUMANS

To investigate the utilization of nutrients by malignant tumors in hum ans, the balances of energy-yielding substrates and amino acids across colonic carcinomas were assessed in 17 patients during surgery. Blood samples were taken from an artery and the main tumor-draining vein, w hich was also used for determining tumor blood flow (direct venous out flow technique). Additionally, the substrate exchange by peripheral ti ssues was studied (femoral arteriovenous differences, venous occlusion plethysmography). Mean blood flow was greater in the carcinomas than in the leg tissues (43.2 versus 2.5 ml/100 ml/min; P < 0.001). There w as a negative correlation between tumor blood flow and tumor weight (r = -0.87; P < 0.001). Glucose net uptake and lactate release by the ma lignancies exceeded the peripheral exchange rates 30- and 43-fold, res pectively (mean values different at P < 0.001). The molar ratio of lac tate output to glucose consumption was 0.78 in the tumors and 0.48 in the leg tissues (P < 0.05). Regarding free fatty acid and ketone body balances, no significant tumor-periphery differences were noted. The c arcinomas utilized branched chain amino acids and serine, while alanin e and, in particular, ammonia were released in large amounts. Net glut amine retention was not consistently observed. It is concluded that th e energy metabolism of human colonic carcinomas relies predominantly o n glucose, with fat-derived calories making no appreciable contributio n. The impaired nutritive perfusion of malignant tumors appears to fav or glycolysis and to limit both glucose oxidation and glutaminolysis. The present study has shown that the procedure chosen for the assessme nt of trans-tumor substrate flux rates is a workable and valid model f or analyzing metabolic balances across human colonic cancers in vivo.