Abstract
These experiments were performed to determine the factor(s) that regulate lactic acid production and utilization by rat tumors in vivo. Arteriovenous differences for glucose and lactic, pyruvic, 3-OH-butyric, and acetoacetic acids were measured across "tissue-isolated" Walker 256 sarcocarcinomas and Morris 5123C hepatomas in fasted rats anesthetized with sodium pentobarbital. Twenty-six per cent of the sarcocarcinomas (n = 53) and 48% of the hepatomas (n = 29) utilized blood lactic acid. The remainder released lactic acid into the venous blood. The steady-state rate of glucose consumption was similar in both lactate-producing and lactate-utilizing tumors. The range of lactate concentrations in the blood leaving the tumors was narrower than the range of lactate concentrations in the blood entering the tumors. This difference was caused by tumor lactic acid production at low arterial lactate concentrations and tumor lactic acid utilization at high arterial lactate concentrations. Individual tumors changed from lactic acid production to lactic acid utilization in a matter of minutes in response to an increase in the arterial lactic acid concentration. Mean lactic plus pyruvic acid concentrations and lactic/pyruvic acid ratios in the tumor venous blood were 2.15 +/- 0.22 and 23.4 +/- 3.7 mM, respectively, for Walker sarcocarcinoma 256 (n = 18) and 1.28 +/- 0.13 and 48.1 +/- 5.1 mM, respectively, for hepatoma 5123C (n = 11). The results suggest: that a steady-state lactic plus pyruvic acid concentration and lactic/pyruvic acid ratio are maintained in the tumor cell cytoplasm by the active glycolytic pathway and by lactic acid dehydrogenase; that the tumor intracellular concentrations equilibrate with the arterial blood and that the tumor steady state is expressed in the tumor venous blood; and that tumor lactic acid production or utilization results from the equilibration between the variable arterial lactic acid concentration and the more constant tumor intracellular steady-state lactic acid concentration. Since the arterial lactate concentration may be less than, greater than, or equal to the intracellular steady-state concentration, an individual tumor may produce, utilize or neither produce nor utilize lactic acid.
Highlights
Factor(s) that regulate lactaiccid production and utili- rat tumors in vivo (1,2) we found that some tumors released zation by rat tumors in vivo.Arteriovenous differences while others utilized blood lactic acid
The results show that movement of lactrations in theblood leaving the tumors wansarrower tate from either arterial blood to tumor or from tumor to than the range of lactate concentrations in the blood venous blood is down a lactic acid concentration gradient; entering the tumors
We found that each tumor type imposed on the venous blood a defined range of lactic acid concentrations and a nearly constant lactic/pyruvic acid ratio
Summary
Steady state is expressed in the tumor venous blood; Mason Research Institute, Worcester, MA These tumors have been and 3) that tumor lactic acid production or utilization carried in this laboratory for about 6 years. Blood Sample Preparatwnand Assay-Neutralized perchloric acid nically possible to measure arteriovenous differences across a extracts of arterial and venousbloodwere prepared as described “tissue-isolated” tumorin viuo in the absence of surgical earlier (1,2). Lactic Acid Production and Utilization in Rat Tumors in Expression and Evaluation of Results-For interpretation of the Vivo-Fig. 1shows the relationship between the host arterial arteriovenous difference measurements, we assumed that the tumor and tumor venous whole blood lactic acid concentrations in was in a steady state with regard tonutrient supply and metabolism and that this steady state continued duringthe 2- or 5-min period of sample collection. Except for one high lactateproducing and one low lactate-utilizing tumor, the venous whole blood lactic acid levels ranged from about 1to 4 mM
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