Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Uridine 5'-diphosphoglucuronic acid-fortified hepatic microsomes from dogs, rats, or humans rapidly metabolized [3H]-N-hydroxy-2-naphthylamine (N-HO-2-NA) to a water-soluble product that yielded 98% of the parent N-hydroxy amine upon treatment with beta-glucuronidase. The metabolite was identified as N-(beta-1-glucosiduronyl)-N-hydroxy-2-naphthylamine from ultraviolet, infrared, and mass spectral analyses of the glucuronide and its nitrone derivative. Incubation of N-hydroxy-1-naphthylamine (N-HO-1-NA), N-hydroxy-4-aminobiphenyl (N-HO-ABP), or the N-hydroxy derivatives of 2-aminofluorene, 4-aminoazobenzene, or N-acetyl-2-aminofluorene with uridine 5'-diphosphoglucuronic acid-fortified hepatic microsomes also yielded water-soluble products. beta-Glucuronidase treatment released 80 to 90% of the [3H]-NHO-1-NA and [3H]-N-HO-ABP conjugates as tritiated ether-extractable derivatives. N-HO-1-NA, N-HO-2-NA, and N-HO-ABP and the glucuronides of these N-hydroxy arylamines were relatively stable and nonreactive near neutral pH. At pH 5, the N-glucuronide of N-HO-2-NA and the presumed N-glucuronides of N-HO-1-NA and N-HO-ABP were rapidly hydrolyzed to the N-hydroxy arylamines that were then converted to reactive derivatives capable of binding covalently to nucleic acids. These data support the concept that arylamine bladder carcinogens are N-oxidized and N-glucuronidated in the liver and that the N-glucuronides are transported to the urinary bladder. The hydrolysis of the glucuronides to N-hydroxy arylamines and the conversion of the latter derivatives to highly reactive electrophilic arylnitrenium ions in the normally acidic urine of dogs and humans may be critical reactions for tumor induction in the urinary bladder.
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PMID:Hepatic microsomal N-glucuronidation and nucleic acid binding of N-hydroxy arylamines in relation to urinary bladder carcinogenesis. 1 29

In vitro transformation of BHK 21/13 cells by chemical carcinogens is reported. The hamster cells were treated with MCA, BP, 4-NQO and 5-azaCR at various concentration and duration of treatment. The morphological, karyological and growth characteristics of cell lines were investigated. Search for RNA tumor viruses in transformed cells using 3H-uridine labeling, detection of DNA polymerases, electron microscopy investigations failed to detect presence of C-type virus particles.
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PMID:Transformation of BHK 21/13 cells by chemical carcinogens and mutagens. 5 82

Uridine 5'-diphosphate-galactose:glycoprotein galactosyltransferase activity was demonstrated in homogenates of normal ovary and ovarian epithelial adenocarcinomas. The specific activity of the enzyme in ovarian tumors was 3 to 5 times higher than in normal ovaries when the enzyme was assayed under identical conditions. The glycoprotein fetuin, from which terminal sialic acid and penultimate galactose were removed (fetuin minus N-acetylneuraminis acid and galactose), acted as an excellent exogenous acceptor. Galactosyltransferase from normal ovary and ovarian tumor cells had similar properties. Both required Mn2+ and Triton X-100 and had broad pH optima between 5.5 and 7. Galactosyltransferase activity was also measured in serum samples from ovarian cancer patients and normal healthy individuals in the presence of fetuin minus N-acetylneuraminic acid and galactose as exogenous acceptor. The enzyme levels were significantly elevated in the sera of ovarian cancer patients as compared to normal controls. The differences in the levels of this enzyme in the tissues and sera of normal individuals and ovarian cancer patients were not due to differential levels of the degrading enzymes such as uridine 5'-diphosphate-galactose pyrophosphatase or beta-D-galactosidase. Serial determinations were carried out on the sera of 5 ovarian cancer patients over a long period of time. The serum level of galactosyltransferase activity appeared to correlate with tumor volume as well as with the clinical status of the patient, which suggests possible leakage of the tumor enzyme into the host sera. Serial determination of this enzyme level in ovarian cancer patients seems promising in measuring tumor progression or success of therapeutic approaches.
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PMID:Uridine 5'-diphosphate-galactose:glycoprotein galactosyltransferase activity in the ovarian cancer patient. 5 28

The in vitro effect of 5-aza-2'-deoxycytidine (5-aza-CdR) on cytotoxicity and macromolecular synthesis in A(T1)C1-3 hamster fibrosarcoma cells was investigated. The in vitro concentrations that produce 50% cell kill for 5-aza-CdR were about 1.0 and 0.01 microng/ml for a 2- and 24-hr exposure, respectively. 5-aza-CdR inhibited the growth of the fibrosarcoma cells by 40% at a concentration of 0.05 microng/ml. Deoxycytidine, but not cytidine, was a potent antagonist of the cytotoxicity produced by 5-aza-CdR. At cytotoxic concentrations 5-aza-CdR did not appear to inhibit DNA, RNA, or protein synthesis during a 1-hr incubation as measured by the incorporation of radioactive thymidine, uridine,, or leucine into acid-insoluble material. At a concentration of 10 microng/ml, 5-aza-CdR stimulated the incorporation of radioactive thymidine into DNA by more than 50%. These results indicate that 5-aza-CdR is a very potent cytotoxic agent to tumor cells in vitro at concentrations that do not inhibit macromolecular synthesis.
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PMID:In vitro cytotoxic and biochemical effects of 5-aza-2'-deoxycytidine. 6 84

The retrovirus designated RPMI8226V (isolated from human myeloma cells RPMI8226) has been characterized with respect to its morphological, biochemical and immunological properties as well as its propagation in various animal and human cells. The myeloma cells RPMI8226 produce intracytoplasmatic A-type particles and extracellular particles. The extracellular particles have been classified as immature particles with translucent core center, typical mammalian C-type virus particles and C-type particles with intermediate membrane. However, the budded particles in secondarily infected human neoplastic cells contained complete doughnut-shaped nucleoids. This type of budding is rather characteristic for B-type particles. The 3H-uridine labeled RPMI8226 viral particles have a buoyant density 1.17 g/ml in sucrose gradient containing high molecular weight RNA and the distribution of viral structural proteins in SDS-PAGE is characteristic for oncornaviruses. The internal structural proteins according to MW are ranged from 13 000 to 30 000 daltons. The virus contains a magnesium-dependent reverse transcriptase. The cellular homogenate and viral concentrate from RPMI8226 cultures do not react with antibodies against ALSV, MuLV, FeLV, RD114, MP-MV and SiSLV. The only reaction was scored with anti BLV antibodies. However, anti BLV serum inhibiting the reverse transcriptase activity of BLV to 60% does not cross-react with the reverse transcriptase of RPMI8226V. In contrast to BLV concentrates, neither XC nor KC cells show syncytia formation by RPMI8226V. The RPMI8226V replication is restricted to human tumor and normal human glia-like cells. The possible origin of the virus is discussed.
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PMID:The retrovirus particles in human myeloma cells RPMI8226: morphological, biochemical, immunological and infective transmission studies. 8 Jul 55

From human mycosis fungoides tumor-derived cell lines, Mycoplasma hyorhinis was isolated. This mycoplasma shared the following characteristics with retroviruses: uptake of 3H-uridine, but not of 3H-thymidine in cell culture; banding at 1.16 g/ml sucrose density and partial shift to retrovirus core density position (approximately equal to 1.24 g/ml) after detergent treatment; incorporation of 3H-TMP into high molecular weight material in standard reverse transcriptase assays with the template-primer poly (A) . (dT)12. On the other hand, the specific reverse transcriptase reaction of retroviruses with poly(A) . (dT)12 and poly(C) . (dG) approximately 16 was almost completely abolished in the presence of the mycoplasma. Thus, M. hyorhinis may interfere with identification and isolation procedures for retroviruses.
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PMID:Simulation and prevention of retrovirus--specific reactions by mycoplasmas. 8 23

By optimal hormonal treatment the production of exogenously transmitted MMTV can be stimulated in vitro to different degrees, depending on cultivation conditions and origin of tumor cells. Moreover, after appropriate hormonal treatment, endogenous MMTV-Y can be rescued from primary cell cultures derived from dimethyl benzanthracene- and hormone-induced C57BL/10 mouse mammary adenocarcinoma, as determined by reverse transcriptase assay, distribution of 3H-uridine-labelled viral particles, immunofluorescence, and electron microscopy. On the contrary, all attempts to rescue MMTV-Y from cultures derived from urethane-induced C57BL/10 tumors failed. These data indicate that upon syncarcinogenic action of non-viral carcinogenes, estrogen and prolactin, the MMTV-Y genome can be expressed in mammary gland parenchymatous cells, which in turn may result in cell transformation. The full MMTV-Y gene expression occur after appropriate hormonal stimulation of the C57BL/10 mammary cancer cells in vitro.
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PMID:Hormone-responsive genes of the mouse mammary tumor virus. 9 6

Urine samples of normal male Fischer rats or rats fed 0.2% N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide for 6,8 or 30 weeks were collected and centrifuged 50 weeks after beginning treatment. After being sonicated and assayed (with purified desialylated ovine submaxillary mucin as acceptor glycoprotein), the exfoliated bladder cells obtained from the urines of treated rats showed uridine 5'-diphosphate galactose:glycoprotein transferase activity. The specific enzymatic activity of the enzyme from cells of 30-week-treated rats was about 10 times higher than from normal rats. The enzyme from cells of hyperplastic rats (treated 6 or 8 weeks) was only slightly higher in specific activity than that of normal rats. A similar was obtained at a later stage of bladder tumor induction, when the urines from 30-week-treated rats contained blood. A correction was made for protein contributed by the blood clot. The possibility that the blood clot contributed galactosyl transferase activity was excluded. Activity of the enzyme was detected in normal rat bladder tissue and in normal human urine.
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PMID:Uridine 5'-diphosphate galactose: glycoprotein galactosyl transferase activity in exfoliated bladder epithelial cells in rats fed N-(4-(5-nitro-2-furyl)-2-thiazolyl) formamide. 9 27

With series of transplanted tumors, the activities of different cytostatic agents which directly influence the metabolism of nucleic acids (Actinomycin D, adriamycin, daunomycin, 5-fluorouracil, procarbazine, trenimon) was measured by determining 3-H-uridine incorporation in short-term (3hrs) incubations of tumor cell suspensions. Data obtained could be used to predict the response of each tumor to particular cytostatic agents in vivo. The activities of the cytostatic agents as determined using long-term tissue cultures (time of exposure of tumor cells to cytostatic agent 48 hrs were comparable to those obtained with the short-term test. In long-term cultures, determination of cell numbers gave results similar to those obtained by morphological evaluation. In SHORt-term test, differing sensitivities of tumors to cytostatics could be detected.
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PMID:Sensitivity tests of tumors to cytostatic agents. I. Comparative investigations on transplanted tumors in vivo and in vitro. 12 19

The effects of estrogens on transport and incorporation of amino acids into the R3230AC mammary adenocarcinoma were studied in vivo and in vitro. Dissociated tumor cells from ovariectomized rats, like those from diabetic rats, displayed elevated transport of proline, representing entry by the A system; transport of phenylalanine (L system) was unaltered, as was glucose transport and its utilization. Administration of estradiol valerate decreased the entry of proline into tumor cells from intact, diabetic, or ovariectomized animals; the response to the steroid hormone was greater in ovariectomized or diabetic rats compared to intact animals. The time course of the effects of estrogen treatment was examined in diabetic rats. By 72 hr, transport of both proline and leucine was significantly decreased; incorporation of leucine into proteins and uridine into RNA was significantly reduced by 24 hr after injection of estradiol valerate. The effects of estrogen in vivo to reduce transport of amino acids and their incorporation into proteins appeared to correlate with the reduced tumor growth observed. Experiments were performed to examine the effects of 17 beta-estradiol in vitro on amino acid transport into dissociated cells from ovariectomized or diabetic rats. Under these experimental conditions, 17 beta-estradiol (10(-6)M) inhibited proline transport with little or no effect on leucine transport in cells from ovariectomized rats; in cells from diabetic rats, proline transport and leucine incorporation were significantly reduced by estradiol, whereas phenylalanine transport was slightly inhibited (approximately 20%). The effect of estradiol in vitro was also manifest in tumor cells obtained from diabetic rats treated in vivo with estradiol valerate; estradiol in vitro caused a further reduction in proline transport but not in leucine transport, results that imply some specificity to the action of estrogen on the A system. Since we had earlier shown that insulin action on transport in these tumor cells were directed towards the A system, we examined the effects of insulin, estradiol, and their combination in vitro on proline and leucine transport. Insulin (10(-8) M) stimulated proline transport; 17 beta-estradiol, at a selected lower level of 10(-8) M, inhibited proline transport. When both were added in vitro, estradiol (10(-8 M) was capable of significantly reducing the insulin (10(-8) M)-induced increase in proline transport. Leucine transport was not altered in any of these experiments. Together, these data suggest that estrogens are capable of inhibiting amino acid transport into the R3230AC mammary carcinoma, an effect that is compatible with reduced tumor growth. The possible relationship of estrogen and insulin at the level of amino acid transport remains to be elucidated.
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PMID:Effects of estrogen to alter amino acid transport in R3230AC mammary carcinomas and its relationship to insulin action. 15 4


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