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R T Dauchy

Publications and source records attributed to R T Dauchy.

28 records · Page 2Linked to original sources
PubMed1986

Stimulation of tumor growth in adult rats in vivo during an acute fast.

These experiments investigate an increase in tumor growth that occurs in adult rats in vivo during an acute fast. The effects of feeding, fasting, and underfeeding on the growth of Morris hepatomas 5123C and 7288CTC in Buffalo rats and of Walker carcinoma 256 and Jensen sarcoma in Sprague-Dawley rats were studied. Animals were matched for tumor size and growth during a period of ad libitum feeding preceding the fasting or underfeeding. Tumor growth was documented by increased size and incorporation of [methyl-3H]thymidine into tumor DNA. Fasting increased the rate of growth of the tumors 3 to 4 times over that measured in fed rats. This effect began during the first day of fasting and ended abruptly on refeeding. After refeeding tumor growth slowed to the rate in fed rats. Tumors from fed or fasted rats were not different in cellularity or dry weight/g wet weight. A positive growth response in the tumor required lipolysis and ketosis in the host. No stimulation was observed during an acute fast in either immature rats or in mature rats whose weights had been reduced by underfeeding. These animals have small fat stores and show no increase in arterial blood free fatty acid or ketone body concentrations during an acute fast. Finally, underfeeding of adult rats raised the blood concentrations of these nutrients to values that were intermediate between those in fasted and fed rats. Tumor growth rates in these rats were intermediate between those in fasted and fed rats. The results support the proposal that an increase in availability of free fatty acids and/or ketone bodies is the stimulus that increases the rate of tumor growth during an acute fast.

Animals↗
PubMed1986

Preparation of "tissue-isolated" rat tumors for perfusion: a new surgical technique that preserves continuous blood flow.

A surgical technique for preparing "tissue-isolated" rat tumors for perfusion was developed that ensures continuous blood flow to the tissue. The tumor may be perfused in situ or ex vivo. Tumor venous blood flow, tumor glucose and lactic acid metabolism, as well as host animal respiration and core temperature, were unchanged during the procedure. Following addition of 14C-D-Glucose to the tumor afferent blood, all radioactivity appeared in the tumor venous blood. None appeared in the host systemic blood, indicating complete separation of tumor and host vasculature during in situ perfusion.

Animals↗
PubMed1986

In vivo lactate production and utilization by Jensen sarcoma and Morris hepatoma 7288CTC.

These experiments were designed to determine the characteristics of lactic acid utilization and production in vivo in Jensen sarcoma and Morris hepatoma 7288CTC. Arteriovenous differences for lactic and pyruvic acids, glucose, and the ketone bodies were measured across "tissue-isolated" tumors growing in fed and fasted rats. Lactic acid was utilized (n = 18), produced (n = 24), or neither utilized nor produced (n = 1) by the tumors. Net tumor lactate production or utilization did not depend on the mean rate of glucose utilization which was the same in the lactate-utilizing and -producing tumors. For the lactic acid-utilizing tumors, the mean arterial whole blood lactate concentration entering the tumor was 3.47 +/- 0.39 mM, and the concentration in the tumor venous blood was 2.31 +/- 0.25 mM. For the lactic acid-producing tumors, the mean arterial lactic acid concentration was 1.29 +/- 0.10 mM, and the tumor venous blood concentration was 2.19 +/- 0.19 mM. Thus, both lactate-producing and lactate-utilizing tumors showed identical rates of glucose utilization and identical lactic acid concentrations in the venous blood leaving the tumors. Metabolite levels were also measured in tumors that were freeze clamped in situ immediately following collection of the arterial and tumor venous blood samples. The lactic acid content in the tumor mass (corrected for total tumor water) and the concentration in the tumor venous blood plasma were nearly identical, suggesting that the lactate concentrations in the tumor cells and tumor venous blood are at equilibrium. Transport of lactic acid between arterial plasma and tumor or between tumor and venous plasma was always down a concentration gradient; net lactate uptake and release in these tumors followed the law of mass action. High lactate concentrations were not observed in the Jensen sarcomas or in the venous blood leaving these tumors, and we were unable to confirm earlier studies indicating that Jensen sarcomas are consistently high net lactate producers in vivo.

Animals↗
PubMed1985

Regulation of lactate production and utilization in rat tumors in vivo.

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.

Animals↗
PubMed1983

Ketone body, glucose, lactic acid, and amino acid utilization by tumors in vivo in fasted rats.

Arteriovenous differences for acetoacetate, beta-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 beta-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 beta-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 beta-hydroxybutyrate. An average of 52% of the acetoacetate and 30% of the beta-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.

3-Hydroxybutyric Acid↗
PubMed1980

Mitochondrial malic enzymes. An association between NAD(P)+-dependent malic enzyme and cell renewal in Sprague-Dawley rat tissues.

The activities of the mitochondrial NAD(P)+- and NADP+-dependent malic enzymes were measured in 11 tissues of the male Sprague-Dawley rat. The NAD(P)+-dependent malic enzyme was present in small intestinal mucosa, spleen, thymus, lung, and testis. Each of these tissues contain cells that are undergoing active rates of renewal. The NADP+-dependent malic enzyme was not confined to tissues undergoing cell renewal, and was present in mitochondria from brain, skeletal, and heart muscle, kidney, and lung and testis. Both enzymes were absent or at a low activity in normal and regenerating liver. The results support, and extent to nonneoplastic tissues, our proposal that cells which show active and sustained rates of renewal contain the NAD(P)+-dependent malic enzyme and have a unique intramitochondrial pathway for malate oxidation (Sauer, L.A., Dauchy, R.T., Nagel, W.O., and Morris, H.P. (1980) J. Biol. Chem. 255, 3844-3848).

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