Walker 256 종양에 있어서 C14-포도당 및 C14-젖산의 산화대사

Abstract

Tissue homogenates of Walker 256 tumor were incubated separately in medium containing 04-1-glucose, 0 46- glucose, OL1-lactate, OL2-lactate, and C~3-lactate in order to observe' the oxidative metabolism of each carbon of substrates which labelled by 0 4• Glucose and lactate media, in which tissue homogenates were incubated, were kept at a concentration of 200mg% and 50mg%, respectively. At the end. of 3 hours incubation, respiratory CO2 samples trapped by alkaline which was placed in the center well of the incubation flask were analyzed for total CO2 production rates and their radioactivities. The tissue homogenate samples after incubation were analyzed for their concentrations of glucose, lactateand pyruvate. Calculations were made on the glucose consumption rate and accumulation rates of lactate and pyruvate. The following results were obtained. 1. In the tissue homogenate, which was incubated with OLglucose as a substrate, total CO2 [production rate averaged 10. 0±2.1 J.lM/hr/gm and CO2 productions from C-1 and C-6 carbon of glucose were means of 23.1 and 2. 6% respectively. 2. Glucose uptake rate in the OLglucose incubation experiment was mean of 14. 3±2. 9 J.l M/hr/grn. The fraction of glucose oxidized into C~ to total glucose uptaked (RGD C02) was only 0.7%. On the other hand, lactate and pyruvate accumulation rates averaged 14. 1 ±3.4 and O.33±0. 6 pM/hr/ gm, respectively, Assuming: that these 3 carbon compounds appeared in the medium were derived from glucose, the relative glucose disappearance rete into lactate(RGDt.) was 48. 9% and RGDi> was 1. 29;}. Therefore, abouth 50; 8% of total glucose uptaken were accounted for by conversion into. respiratory CO2• lactate and pyruvate. 3. The oxidative pathway of glucose in the tumor tissue was analyzed from the values of relative specific activities which were obtained in the OL1 and 0 4- & -glucose incubation experiments. It was found that 11. 3% of CO2 deriven from glucos were via the principal EMP-TCA cycle and the remainder were via the alternate pathway such as HMP. 4. In the Of-lactate incubation experiments, total CO2 production rate was mean of 10.2 ,uM/hr/gm which showed same order in value obtained in the C14-glucose incubation. Lactate was accumlated to about O. 244 mg/hr/ gm from endogenous source in every run of experiments. The pyruvate accumulation rate was mean of O.045 mg/ hr/gm. Respiratory C14 O2 yield from C-1 carbon of lactate was 13.8-2.3% of total CO2 production rate and this proportion was larger than those from C-20r C-3 carbon of lactate whose values showed 3.78-1.1 and 7.97-2.1, respectively. It shows that carboxyl carbon of lactate contributes a larger proportion in producing respiratory CO2 than 2 and 3 carbons of lactate. From the data described above, it was assumed that anaerobic glycolysis proceeds normally, resulting in the accumlation of lactate in the Walker 256 tumor but farther oxidation via the TCA cycle was remarkably inhibited and almost all of oxidative energy from glucose was released by alternate pathway such as HMP.