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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitochondria isolated from spontaneous and transplanted mammary adenocarcinomas of two strains of mice were compared, by various biochemical criteria, to mitochondria from mammary glands of midpregnant or hormonally stimulated, cancer-free mice. The specific activities of several mitochondrial enzymes including cytochrome oxidase, alpha-glycerophosphate oxidase, and succinate dehydrogenase were twofold to threefold lower, whereas the activity of monoamine oxidase was two fold higher in tumor mitochondria. Malate dehydrogenase, adenylate kinase, and NADH oxidase showed similar levels of activity in tumor and midpregnant mammary gland mitochondria. In addition, mitochondrial polypeptide composition was analyzed by electrophoresis on sodium dodecyl sulfate-urea polyacrylamide gels. Midpregnant mammary gland and mammary tumor mitochondria were similar in polypeptide composition; however, several differences were observed. A high-molecular-weight polypeptide, present in mid-pregnant mammary gland mitochondria was absent from tumor mitochondria. Also, tumor mitochondria contained an additional high-molecular-weight polypeptide not found in the midpregnant mammary gland. There were numerous differences in the relative proportions of many polypeptides common to both tumor and midpregnant mammary gland mitochondria.
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PMID:Biochemical studies on mitochondria isolated from Normal and Neoplastic Tissues of the Mouse Mammary Gland. 17 82

The activity of the malate-aspartate shuttle for the reoxidation of cytoplasmic reduced nicotinamide adenine dinucleotide (NADH) by mitochondria was assessed in six lines of rodent ascites tumor cells (two strains of Ehrlich ascites carcinoma, Krebs II carcinoma, Novikoff hepatoma, AS-30D hepatoma, and L1210 mouse leukemia). All the tumor cells examined showed mitochondrial reoxidation of cytoplasmic NADH, as evidenced by the accumulation of pyruvate when the cells were incubated aerobically with L-lactate. Reoxidation of cytoplasmic NADH thus generated was completely inhibited by the transaminase inhibitor aminooxyacetate. The involvement of the respiratory chain in the reoxidation of cytoplasmic NADH was demonstrated by the action of cyanide, rotenone, and antimycin A, which strongly inhibited the formation of pyruvate from added L-lactate. Compounds that inhibit the carrier-mediated entry of malate into mitochondria, such as butylmalonate, benzenetricarboxylate, and iodobenzylmalonate, also inhibited the accumulation of pyruvate from added L-lactate by the tumor cells. The maximal rate of the malate-aspartate shuttle was established by addtion of arsenite to inhibit the mitochondrial oxidation of the pyruvate formed from added lactate. The capacity of the various tumor lines for the reoxidation of cytoplasmic NADH via the malate-aspartate shuttle approaches 20% of the total respiratory rate of the cells and thus appears to be sufficient to account for the mitochondrial reoxidation of that fraction of glycolytic NADH not reoxidized by pyruvate and lactate dehydrognenase in the cytoplasm.
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PMID:Occurrence of the malate-aspartate shuttle in various tumor types. 17 6

Measurements of respiration, CO2 and lactate production, and changes in the levels of various key metabolites of the glycolytic sequence and tricarboxylic acid cycle were made on five lines of rodent ascites tumor cells (two strains of Ehrlich ascites tumor cells, Krebs II carcinoma, AS-30D carcinoma, and L1210 cells) incubated aerobically in the presence of uniformly labeled D-[14C]glucose. From these data, as well as earlier evidence demonstrating that the reduced nicotinamide adenine dinucleotide (NADH) shuttle in these cells requires a transaminase step and is thus identified as the malate-aspartate shuttle (W.V.V. Greenhouse and A.L. Lehninger, Cancer Res., 36: 1392-1396, 1976), metabolic flux diagrams were constructed for the five cell lines. These diagrams show the relative rates of glycolysis, the tricarboxylic acid cycle, electron transport, and the malate-aspartate shuttle in these tumors. Large amounts of cytosolic NADH were oxidized by the mitochondrial respiratory chain via the NADH shuttle, comprising anywhere from about 20 to 80% of the total flow of reducing equivalents to oxygen in these tumors. Calculations of the sources of energy for adenosine triphosphate synthesis indicated that on the average about one-third of the respiratory adenosine triphosphate is generated by electron flow originating from cytosolic NADH via the malate-aspartate shuttle.
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PMID:Magnitude of malate-aspartate reduced nicotinamide adenine dinucleotide shuttle activity in intact respiring tumor cells. 19 30

The distribution of simian virus 40 large tumor antigen in subcellular fractions from simian virus 40-transformed hamster (H-50) and mouse (VLM) cells and from simian virus 40-infected monkey cells was determined. Solubilized [(35)S]-methionine- or (32)P(i)-labeled surface membrane and nuclear fractions were prepared, immunoprecipitated with hamster anti-T serum, and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Tumor antigen with an apparent molecular weight of approximately 96,000 was detected in both subcellular fractions. Minor components of approximately 68,000 and approximately 56,000 with anti-T reactivity which labeled with [(35)S]methionine were also detected in both fractions from H-50 cells, as were components of approximately 140,000 and approximately 56,000 from VLM cells. The 56,000 component appeared to be greatly reduced in (32)P(i)-labeled surface membrane fractions. Normal cells or cells transformed with a heterologous agent, such as polyoma virus or a chemical carcinogen, lacked immunoprecipitable tumor antigen. Cell fractionation was monitored by [(3)H]thymidine labeling, NADH-diaphorase activity, and Na(+)-K(+)-dependent ATPase activity. These analyses revealed only trace contamination of surface membranes by nuclei, extremely low levels of nuclear rupture during homogenization, and an approximate 10-fold enrichment of surface membrane. Reconstruction experiments demonstrated that soluble tumor antigen failed to associate or copurify with surface membranes during fractionation procedures. These results indicate the presence of a protein in the plasma membrane of cells transformed or infected by simian virus 40 that is immunologically indistinguishable from nuclear tumor antigen.
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PMID:Subcellular Localization of simian virus 40 large tumor antigen. 22 15

The previously observed alterations in the energy transducing system of rat liver mitochondria during 3'-methyl-4-(dimethylamino)azobenzene (3'-Me-DAB) carcinogenesis were investigated using aliphatic dicarbonyl compounds as molecular probes and the effect of temperature on the membrane-linked NADH-indophenol reductase. The vicinal diketone, diacetyl, uncouples oxidative phosphorylation in normal rat liver mitochondria while the higher diketones, acetylacetone and acetonylacetone, are increasingly less effective in that order; diacetyl totally abolishes respiratory control with substrates the oxidation of which involves the NADH leads to CoQ segment, but only partially with succinate which bypasses this segment. Diacetyl, likewise, uncouples oxidative phosphorylation in liver mitochondria from rats fed 3'-Me-DAB, but the mitochondria are most resistant to this uncoupling (in terms of the P/O ratio) at the time period when the respiratory control index (determined in the absence of diacetyl) is at the dye-induced minmum. This time period is at 3 to 4 weeks of dye administration, representing the cumulative dose for tumorigenesis threshold. At this threshold period of feeding 3'-Me-DAB, discontinuities in the Arrhenius plot of the mitochondrial membrane-localized NADH-indophenol reductase appear, with a return toward the control state (no break) at 8 weeks, only to reappear in the plot of the enzyme from tumor mitochondria, suggesting sequential membrane phase transitions in the mitochondria during azo dye carcinogenesis.
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PMID:Mitochondrial membrane-linked reactions in carcinogenesis: change in steroselective uncoupling of oxidative phosphorylation by aliphatic dicarbonyls and in the Arrhenius plot of NADH-indophenol reductase. 40 68

The plasma membrane of the Ehrlich ascites tumor cell contains an NADH dehydrogenase. This activity was shown not to be due to contamination by other subcellular membranes. A variety of electron acceptors have been compared as to rate with the following result: ferricyanide greater than cytochrome c greater than cytochrome b5 greater than glyoxylate greater than dichlorophenolindophenol. Oxygen acceptance could not be detected. The optimum assay temperature and pH ranges were 30--40 degrees C and pH 6--8, respectively. With respect to either NADH or ferricyanide, the kinetics yielded linear double-reciprocal plots. Inhibition of the enzyme by sulfhydryl reagents could be blocked by excess NADH. Detergents such as Triton X-100 or cholate resulted in solubilization of the enzymatic activity, but phospholipase A2 did not. The activity differed from that of the mitochondria in that it was not inhibited by rotenone or antimycin A. The possible involvement of NADH oxidation in the energetics of plasma membrane transport is discussed.
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PMID:Electron-transferring enzymes in the plasma membrane of the Ehrlich ascites tumor cell. 42 30

Anaerobic culture conditions (95% argon/5% CO2) caused a slightly greater increase in total lipids of Ehrlich ascites tumor cells than a gas phase of 20% O2, 75% N2, 5% CO2. Whereas the rate of [U-14C]acetate incorporation into total lipids and lipid-subclasses rose markedly in the absence of oxygen, a drastic decrease of [U-14C]pyruvate and [1-14C]octanoate incorporation as well as a 30% reduction of 3H incorporation into lipids from tritiated water were observed under these conditions. Since profound changes in the metabolic state of cells cause alterations in the specific activity of the acetyl-CoA pool but do not alter the specific activity of intracellular water, this precursor is considered to be an adequate monitor for lipogenesis under aerobic and anaerobic culture conditions. Therefore, it is concluded that Ehrlich ascites tumor cells are not able to reoxidize NADH/NADPH in the absence of oxygen by a stimulation of biosynthesis of fatty acids as is discussed to be the case in normal cells. The slight increase in total lipids of anaerobically cultured cells seems to be the result of an imbalance between normal uptake and impaired utilization of lipids from serum-supplemented culture medium.
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PMID:Lipogenesis in Ehrlich ascites tumor cells under anaerobic culture conditions. 52 49

5-Chloro-2,3-dimethyoxy-6-octylmercapto-1,4-benzoquinone (NSC 252188) and 2,3-dimethoxy-5-hydroxy-6-phytyl-1,4-benzoquinone (NSC 277818) inhibited the human cell lines 4265 and K 562c, and the experimental animal tumor line W256; they also showed antitumor activity against Walker carcinosarcoma 256 in rats with cures; they also inhibited the mitochondrial coenzyme Q10-enzymes, succinoxidase and NADH-oxidase. 5-Chloro-2,3-dimethoxy-6-n-dodecylmercapto-1,4-benzoquinone (NSC 220334) and 5-chloro-6-omega-cyclohexylhexylmercapto-2,3-dimethoxy-1,4-benzoquinone (NSC 238136) were also active against the K 562c cell line and showed cures against the Walker carcinosarcoma 256 in rats.
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PMID:Inhibition of two human tumor cell lines by antimetabolites of coenzyme Q10. 65 3

The activity of NADPH- and NADH-dependent erythrocyte glutathione reductase was determined in rats with Morris 5123 hepatoma at different stages of tumor development (10, 20, 30 and 40 days after transplantation). During the early stage of tumor growth the activity of glutathione reductase with either of these coenzymes was increased. In the late stage of the disease the activity of NADPH-dependent glutathione reductase fell below control values. The obtained results are discussed in the light of previous observations on the effects of this neoplasm on the metabolism of erythrocytes.
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PMID:[Glutathione reductase activity in erythrocytes of rats with transplantable Morris 5123 hepatoma]. 73 12

Methyl-GAG was tested in organotypic cultures of malignant tumors of human and mice. In 3 cases, a reduction of the activity of two oxydoreductases (lactate dehydrogenase and NADH-diaphorase) after treatment with methyl-GAG was observed whereas in 19 other cultivated tumors no change of enzyme activity was induced by methyl-GAG. Electronmicroscopy revealed only minor structural alterations of tumor cells after application of methyl-GAG as compared with control cultures.
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PMID:[Histochemical and ultrastructural investigations on the activity of methylglyoxal (bis)-guanylhydrozan (methyl-GAG) on organ cultures of malignant tumors (author's transl)]. 86 71


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