[Hyperthermia and irradiation for tumor treatment (proceedings)].
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Biomedical subjects
Publications and source records attributed to C Streffer.
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NAD+ glycohydrolase activity located in the nuclear envelope was maximally solubilized by treatment with 0.1--0.2% Triton X-100. The residual activity largely represents the chromatin-associated NAD+ glycohydrolase. Under these conditions the phospholipids were extensively solubilized (over 90%) while leaving the nuclei physically stable, although the nuclear membranes were removed, as shown by electron microscopy. After Triton X-100 treatment, deoxyribonuclease I did not significantly affect the residual NAD+ glycohydrolase activity, although the DNA was completely broken down. This enzyme activity can be released from the nuclear pellet by incubation with phospholipase C. For comparative studies, the glucose 6-phosphatase activity, known to be present in the nuclear envelope, was investigated. Treatment with 0.01% Triton X-100 released 10--20% of the phospholipids, but without solubilizing either glucose 6-phosphatase or NAD+ glycohydrolase. Higher Triton X-100 concentrations (0.1--1.0%) inhibited glucose 6-phosphatase, but not NAD+ glycohydrolase activity. NAD+ glycohydrolase is apparently present in a latent form in the nuclear envelope. Glucose 6-phosphatase, However, shows no such latency.
A correlation between the NAD metabolism and DNA synthesis, that means cell proliferation, was observed in the course of experimental studies using mouse tissues. The present studies revealed a similar correlation also in splenic tissues of patients with Hodgkin's disease. The enzymatic activities of NAD-pyrophosphorylase and NAD-glycohydrolase were measured in detail in isolated cell nuclei. NAD-pyrophosphorylase activity was particularly increased in patients with Hodgkin's disease. A decrease of enzymatic activity was seen following radiation therapy, and especially 24 hours after local irradiation of the spleen with 200 rd(60Co). These studies are in accordance with former results obtained in mice.
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Preimplanted mouse embryos were cultured in an in vitro-system from the two cell stage to blastocysts. In the control cultures about 92% of the incubated embryos developed to blastocysts. When tritiated compounds like tritiated water or tritiated thymidine were present in the incubation medium the number of blastocysts decreased with increased medium tritiated thymidine was about one thousand times more effective than tritiated water. Tritiated thymidine caused a more pronounced division delay than tritiated water which had a strong effect on the blastulation process. Further studies showed that the incorporation of tritiated thymidine into the DNA lead to high concentrations of tritium in the cell nucleus. Dose calculations are performed for the cell nucleus in the case of incubation with tritiated thymidine as well as with tritiated water. The different action of the tritiated compounds can apparently be explained by the specific incorporation of thymidine into the DNA.
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It has been observed that the NAD level is lower in regenerating and growing mouse liver than in resting liver of adult mice. Also it has been found that in proliferating liver the NAD biosynthesis from nicotinamide and nicotinate is unchanged whereas that from tryptophan is reduced. Under these conditions the enzymatic activity of the kynureninase is decreased and the activity of the kynurenine aminotransferase as well as of the tryptophan pyrrolase is not altered. From these and other data of the literature it is concluded that the NAD biosynthesis from tryptophan is important for the regulation of the hepatic NAD level, through this pathway and the NAD degradation nicotinamide is formed which is transported to the non-hepatic tissues to act as a NAD precursor there. The possible interrelation between the NAD metabolism and the DNA synthesis is discussed.
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