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Biomedical subjects

M Tezuka

Publications and source records attributed to M Tezuka.

At least 91 records · Page 5Linked to original sources
PubMed1983

Antitumor effect of 5-fluorouracil in combination with some additives which stimulate the formation of antineoplastic 5-fluorouracil nucleotides.

Both ribose 1-phosphate and deoxyribose 1-phosphate, which were effective in increasing the formation of antineoplastic fluoronucleotides and fluoro-RNA from 5-fluorouracil (5-FU) in the intact cells of Ehrlich mouse ascites tumor, potentiated the antitumor effect of 5-FU. Ethylenediaminetetraacetate, which stimulates the formation of only fluororibonucleotides from 5-FU in intact Ehrlich tumor cells, was ineffective in the potentiation of 5-FU antitumor activity. The relationship between the increased metabolite formation from 5-FU and the antitumor effect of 5-FU is discussed.

Animals↗
PubMed1983

Potentiation of the antitumor effect of 5-fluorouracil by some nucleotides, and their possible role in the potentiation.

Of the various nucleotides tested, adenosine 5'-triphosphate (ATP), guanosine 5'-triphosphate, inosine 5'-triphosphate, and adenosine 5'-monophosphate potentiated the antitumor activity of 5-fluorouracil against Ehrlich carcinoma, while uridine 5'-triphosphate, cytidine 5'-triphosphate, deoxyadenosine 5'-triphosphate, and deoxyguanosine 5'-triphosphate were ineffective. The result of biochemical experiments suggests that ATP, which was used as a representative of the effective nucleotides, was ineffective until it was hydrolyzed to adenosine by nucleotide phosphohydrolases in the ascitic fluid of mice bearing Ehrlich ascites tumor cells, and that the adenosine functioned as a ribose donor for the increased formation of antineoplastic 5-fluoronucleotides. The possible role of the various effective nucleotides and nucleosides was discussed.

Adenosine↗
PubMed1982

Additive formation of antineoplastic 5-fluorouracil nucleosides from 5-fluorouracil by Ehrlich ascites tumor extracts in the presence of ribose 1-phosphate/uridine or deoxyribose 1-phosphate/deoxyuridine.

In order to acquire a biochemical fundamental knowledge on the enhancement of antitumor effect with 5-fluorouracil or its masked derivatives, this investigation was undertaken to determine the amounts of antineoplastic metabolic precursors formed from 5-fluorouracil-6-14C in the presence of various substrates by crude enzyme extracts from Ehrlich mouse ascites tumor cells and normal mouse liver. Combinations of uridine plus ribose 1-phosphate and deoxyuridine plus deoxyribose 1-phosphate were effective for the enhancement of 5-fluorouridine and 5-fluorodeoxyuridine formation, respectively. 5-Fluorouridine and 5-fluorodeoxyuridine are respectively utilizable for the syntheses of the antineoplastic compounds, 5-fluorouridine 5'-triphosphate and 5-fluoro-2'-deoxyuridine 5'-monophosphate. These results suggest that the coadministration of the above substrates together with 5-fluorouracil would be advantageous in the enhancement of the antitumor effect of 5-fluorouracil or its masked derivatives.

Animals↗
PubMed1982

Increased uptake of 5-fluorouracil by Ehrlich ascites tumor cells with some additives and metabolite analysis.

We studied the uptake of radioactive 5-fluorouracil (FUra) by the intact cells of Ehrlich ascites tumor in the presence of various coreactants with FUra such as uridine (Urd), deoxyuridine (dUrd), ribose 1-phosphate (Rib1P), and deoxyribose 1-phosphate (dRib1P). Radioactivity uptake by the cells was increased when FUra-6-14C was incubated with Rib1P or dRib1P, while the uptake was not stimulated with Urd or dUrd. The increased formation of antineoplastic ribo- and deoxyribo-nucleotides of FUra in the acid-soluble fraction was also observed in the same incubation with Rib1P or dRib1P. Also, some detergents, ethylenediaminetetraacetic acid (EDTA), adenosine 5'-triphosphate (ATP), and polyamines were examined. EDTA stimulated the uptake of radioactivity from the FUra by the cells. However, the other compounds exhibited no effect on the uptake of FUra alone or FUra plus dRib1P, except of ATP showing somewhat increase of radioactivity uptake. The above results suggest that the coadministration of FUra together with Rib1P or/and dRib1P, which are stimulants for the formation of FUra-deoxynucleotides from FUra, may be able to potentiate the chemotherapeutic effect of FUra.

Adenosine Triphosphate↗
PubMed1982

Biochemical characteristics of a 5-fluorouracil-resistant subline of P388 leukemia.

A 5-fluorouracil (5-FU)-resistant cell line of P388 mouse leukemia was established by intraperitoneal treatment with the drug. The activities of enzymes responsible for the formation of 5-fluoro-2'-deoxyuridine 5'-monophosphate and 5-fluorouridine 5'-monophosphate from 5-FU, the quantities of 5-FU metabolites, and the permeability to 5-FU were determined in both the 5-FU-sensitive and the resistant cell lines. It was found that the activities of uridine kinase and uracil phosphoribosyltransferase, the initial uptake of 5-FU, and the intracellular levels of 5-FU-nucleotides were all decreased in the resistant cells. However, the initial uptake of 5-FU into cells preincubated with KCN was the same in the sensitive and the resistant cells. These results support the view that the ineffectiveness of 5-FU against the resistant cell line of P388 leukemia can be attributed to decreases in the activities of enzymes responsible for the formation of 5-FU-nucleotides and probably also decreased transport of 5-FU in the resistant cells.

Animals↗
PubMed1980

Increased formation of 5-fluoro-2'-deoxyuridine 5'-monophosphate from 5-fluorouracil in the presence of 2-deoxy-alpha-D-ribose 1-phosphate and 2'-deoxyuridine in Ehrlich ascites tumor cells.

In expectation of the elevated formation of an antineoplastic metabolite from 5-fluorouracil (5FU), we examined the additive effect of 2-deoxy-alpha-D-ribose 1-phosphate (dRib1P) and/or 2'-deoxyuridine (dUrd) upon the formation of 5-fluoro-2'-deoxyuridine (5FdUrd) or proximately more antineoplastic 5-fluoro-2'-deoxyuridine 5'-monophosphate (5FdUMP) from 5FU using a crude extract and the whole cells of Ehrlich tumor cells. The amounts of 5FdUrd formed from 5FU by a crude extract were increased in the presence of dRib1P and dUrd, although it was stimulated much more by dRib1P than by dUrd. In the intact cells, the conversion of 5FU to 5FdUMP was also increased by dRib1P, while the presence both of dRib1P and dUrd enhanced the formation of 5FdUrd rather than that of 5FdUMP. These results suggest that the coadministration of 5FU with dRib1P may increase the chemotherapeutic effect of 5FU.

Animals↗
PubMed1978

[Radiolytic decontamination of Di-n-butyl phthalate from water (author's transl)].

Recently, a considerable amount of phthalic acid esters (PAE), the most widely utilized plasticizer, has been released into and polluted the environment. Since their toxicity and teratogenicity, although fairly low, to experimental animals have recently been shown, the removal of them from the environment, especially from the drinking water, is desirable. As an attempt for the removal, the radiolytic degradation of 7-14C-di-n-butyl phthalate (14C-DBP) in water was investigated at several pHs. Approximately 50% of 14C-DBP (1 ppm aqueous solution) was decomposed by 60Co gamma-irradiation to a dose of 3 X 10(4) rad at pH 7 and the main product was mono-n-butyl phthalate (MBP). At pHs 3 and 11 14C-DBP was more easily radiolyzed and converted to ether-soluble compounds other than MBP or phthalic acid (PA). By irradiation to 10(6) rad 14C-DBP as well as 14C-MBP and 14C-PA, at pH value tested, was almost completely decomposed to volatile or water-soluble substances of possibly low molecular weight. These findings suggest that the gamma-irradiation is effective to make the PAE-polluted water clean.

Chemical Phenomena↗
PubMed1978

Elevation of the salvage synthesis of ribonucleic acid in the rat liver during the induction of hepatoma with 3'-methyl-4-(dimethylamino)azobenzene.

Incorporation of uracil and orotic acid into the ribonucleic acid (RNA) fraction of rat liver during carcinogenesis induced with 3'-methyl-4-(dimethylamino)azobenzene was investigated. Uracil incorporation was found to be gradually elevated during the early stage (about 2 weeks) of the carcinogenesis, although not in the normal rat liver homogenates contacted with the carcinogen for a short hours, and the elevated uptake was maintained until tumor induction. On the other hand, orotic acid incorporation reverted to the original level after a temporary increase during the early stage. In a good agreement with the increased uracil incorporation, activities of both uridine phosphorylase and uridine kinase involved in the salvage pathway of RNA synthesis also increased during the early stage, and their activities in the liver were maintained at elevated levels after discontinuance of the carcinogen feeding. The activity of uridine monophosphate (UMP) pyrophosphorylase, converting uracil to UMP, was not detected during the early stage. Significance of the activation of the salvage pathway of RNA synthesis during the early stage of an axo dye-induced carcinogenesis were discussed.

Animals↗
PubMed1977

Incorporation characteristics of uracil, uridine, and orotic acid into ribonucleic acid of neoplastic cells.

Incorporation of uracil and uridine into ribonucleic acid (RNA) was compared among the ascitic and solid forms of Ehrlich mouse tumor, Morris hepatoma, Rhodamine sarcoma, gastric cancer and ulcer from human patients, and several normal rat tissues. Of these cells tested, the cells of Ehrlich ascites and solid tumors, human gastric cancer and ulcer, and certain tissues of a normal rat showed a considerably high activity. Furthermore, Ehrlich ascites tumor cells indicating a high incorporation activity was also high in activities of both phosphorylase and kinase for uridine, while Rhodamine sarcoma as a representative having a low incorporation activity was considerably low in these two enzymic activities. RNA synthesis from uridine phosphates by Rhodamine sarcoma was maintained to a fairly high extent contrary to its low activities of the phosphorylase and the kinase. Consequently, the low utilization of uracil and uridine by certain tumors was suggested to be due to the extremely low activities of both enzymes.

Adult↗