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각종 인체 암조직의 당의 산화경로 분석

Oxidative Pathway of C<sup>14</sup>-glucose in Various Human Cancer Tissues

Tissue homogenates of 12 kinds of human cancer tissues were incubated separately in medium containing C<sup>14</sup>-1-glucose and C<sup>14</sup>-6-glucose as a substrate in order to observe the oxidative pathway of glucose in the tumor tissues. At the end of 3 hours incubation in the Dubnuff metabolic shaking incubator, respiratory CO<sub>2</sub> samples trapped by alkaling which was placed in the center well of incubation flask were analysed for total CO<sub>2</sub> production rates and their radioactivities. The tissue homogenate samples after incubation were analyzed for their concentrations of glucose, lactate and pyruvate. Calculations were made on the glucose consumption rate and accumulation rates of lactate and pyruvate. Fractionation of oxidative pathway of glucose was carried out by calculating C<sup>14</sup>O<sub>2</sub> yields from C-1 and C-6 carbon of glucose. The following results were obtained. 1. In 12 kinds of human cancer, total CO<sub>2</sub> production rates were less than 8μM/gm except 2 cases. These lower values impressed that oxidative metabolism in the tumor tissues generally inhibited as compared with that in normal tissues. On the other hand, fractions of CO<sub>2</sub> derived from glucose to total CO<sub>2</sub> production rates (RSA) were less than 10% in every case. These facts showed that oxidation of glucose into CO<sub>2</sub> was remarkably inhibited in the tumor tissues. 2. Factions of glucose disappeared into CO<sub>2</sub>, lactate (RGD<sub>L</sub>), pyruvate (RGD<sub>P</sub>) to glucose consumption rates were as follows. RGDco<Sub>2</sub> were less than 2% in cases of in this experiment and RGD<sub>L</sub> showed more than 5% except in 2 cases. These facts showed that anaerobic degradation of glucose into 3 carbon compounds was easily proceeded but further degradation into CO<sub>2</sub> via the TCA cycle was greatly inhibited resulting in accumulation of lactate. There are large variation in values of RGD<sub>P</sub> in different kinds of tumor tissue but relatively higher values in RGDco<Sub>2</sub> were obtained in the tumor tissues as compared with those of normal tissues. 3. The oxidative pathway of glucose in tumor tissues were analyzed from the values of RSA which were obtained in C<sup>14</sup>-1 and C<sup>14</sup>-6-glucose incubation experiments. It was found that 3% of CO<sub>2</sub> derived from glucose were oxidized via the principal EMP-TCA cycle and the remainder were via alternate pathway such as HMP in the liver cancer and values in other cancer tissues were as follows; 4% in the tongue cancer, 6% in the colon cancer, 6% in the lung cancer, 9% in the stomach cancer, 11% in the ovarian cancer, 12% in the neck tumor, 22% in the uterine cancer, 22% in the bladder tumor, 32% in the spindle cell sarcoma and 65% in the brain tumor. These values except later 2 cases showed less than 30% which is the lowest value among the normal tissues. Even in the brain tumor in which showed highest value in the tumor group. It is reasonable to suppose that this fraction was remarkably decreased because values in normal brain tissue was more than 90%. From the above data, it was concluded that in tumor tissues, oxidation of glucose via TCA cycle was greatly inhibited but correlation between degree of inhibited oxidation of glucose via TCA cycle and malignancy of tumor were not clarified in this experiments.

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