Ketone Body, Glucose, Lactic Acid, and Amino Acid Utilization by Tumors in Vivo in Fasted Rats¹

Arteriovenous differences for acetoacetate, β-hydroxybutyrate, glucose, lactic acid, and glutamine and other amino acids were measured across Morris hepatomas 5123C, 7777, and 7288CTCF and Walker sarcocarcinoma 256 in vivo in rats fasted for 2 days. The acetoacetate and β-hydroxybutyrate concentrations in arterial whole blood of fasted tumor-bearing rats were 0.52 ± 0.06 and 1.82 ± 0.19 mm (S.E., n = 38), respectively. Both ketone bodies were utilized by the tumors, and the rates of utilization were directly related to the rates of supply. The mean utilization rates for acetoacetate and β-hydroxybutyrate were 13.9 ± 2.9 (range, 0 to 64; n = 30) and 24.7 ± 4.4 (range, 0 to 145; n = 38) nmol/min/g tumor wet weight, respectively. Eight of the tumors produced acetoacetate, presumably from utilized β-hydroxybutyrate. An average of 52% of the acetoacetate and 30% of the β-hydroxybutyrate carried in the arterial blood was removed during one pass through the tumors. The concentrations of glucose and glutamine in the arterial whole blood of fasted tumor-bearing rats (n = 38) were 6.55 ± 0.3 and 0.76 ± 0.02 mm, respectively; both of these substrates were utilized at rates that were directly proportional to the rates of supply. The mean rates of glucose and glutamine utilization for all tumors in fasted rats were 101 ± 11 (range, 3 to 313) and 8.2 ± 1.1 (range, 0 to 25.1) nmol/min/g tumor wet weight, respectively. Thirty-six % of the glucose and 25% of the glutamine supplied to the tumors was utilized. Comparison (by linear regression and analysis of covariance) of the rates of supply and utilization of glucose and glutamine in tumors growing in fasted versus fed rats indicated that these substrates are utilized more efficiently by tumors growing in fasted animals. Lactic acid was either produced or utilized, depending on the arterial whole-blood concentration. Production or utilization occurred, respectively, when the arterial lactate concentration was less or greater than 1 to 3 mm. The arterial whole-blood amino acids (except glutamine) were utilized at rates that ranged from 1 to 4 nmol/min/g tumor wet weight. The results indicate that energy production for tumor growth in fasted rats is supported, in part, by an increased availability of ketone bodies, by an increased efficiency of utilization of glucose and glutamine, and, under certain circumstances, by utilization of lactic acid.