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)

In short-term experiments TTT (trinitroso-trimethylene-triamine) dissolved in DMSO (dimethylsulfoxide) caused, when orally or intraperitoneally applied, a significant enhancement of the mitotic rate in the adrenal cortex. By long-term studies the carcinogenic action of TTT in DMSO was demonstrated. In female Wistar rats a 100% liver tumor yield was observed following chronic application. After 362 days of treatment cholangiomas had developed, hepatomas and liver carcinomas occurred after 470 days of administration of TTT dissolved in DMSO.
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PMID:[Tumorigenicity of TTT dissolved in DMSO (author's transl)]. 19 Sep 74

Induction of differentiation of a human promyelocytic leukemic cell line (HL60) in culture is accompanied by changes in acid phosphatase (Acpase) activity. The increase in activity is less than twofold when the leukemic cells are stimulated by dimethylsulfoxide (DMSO) to differentiate into metamyelocytes and granulocytes but is eightfold when the cells are stimulated by the tumor-promoting agent 12-0-tetradecanoylphorbol 13-acetate (TPA) to differentiate into macrophage-like cells. Five different isozymes of Acpase were separated by acrylamide gel electrophoresis. Isozyme 1, the most anodal isozyme, was found to be present in undifferentiated, DMSO-treated and TPA-treated cells; isozyme 2 was a very faint band observed both in DMSO- and TPA-treated cells, the isoenzymes 3a and 3b were present only in TPA-induced cells; and isozyme 4, the most cathodal isozyme, was present both in TPA- and DMSO-induced cells. A time sequence study on the appearance of the various forms after TPA treatment indicated that the expression of the isozymes is regulated in an uncoordinated fashion. Acpase activity has been shown by ultrastructural cytochemistry to be localized in the entire rough endoplasmic reticulum (RER) and in areas of the smooth endoplasmic reticulum (SER) located near the Golgi complex in differentiating cells but to be extremely weak, if at all detectable, in undifferentiated promyelocytes.
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PMID:Regulation of acid phosphatase activity in human promyelocytic leukemic cells induced to differentiate in culture. 29

Treatment of Friend leukemia cells with BrdU, the thymidine analog which interferes with DMSO induced differentiation in these cells as well as the expression of differentiated character in many other cell systems, is capable of inducing erythroid differentiation. Globin mRNA, as assayed by hybridization to globin cDNA, increases 2.5- to 30-fold after appropriate treatment with BrdU. This effect was observed with several different subclones of three independent Friend tumor cell lines. After BrdU treatment, globin mRNA content may reach up to 10-20% of the levels in DMSO induced cultures. The induction of erythroid differentiation is also apparent when accumulated heme content or the appearance of benzidine positive cells is monitored. One Friend cell line (745) we examined was not induced by BrdU although it incorporated an amount of BrdU into its DNA comparable to that incorporated by the other cell lines. In addition, BrdU did interfere with DMSO induction in this cell line. These results suggest that two different mechanisms may be operative in regulating erythroid differentiation in Friend leukemia cells. While BrdU interferes with the mechanism activated by DMSO treatment, this analog could independently activate an alternative mechanism.
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PMID:Induction of erythroid differentiation in Friend leukemia cells by bromodeoxyuridine. 64 67

Tetrakis(hydroxymethyl)phosphonium chloride (THPC) and Pyroset TKP, which is the mixed acetate/phosphate of the same phosphonium base, are widely used in flame-retardant cotton fabrics, particularly in children's sleepwear. THPC degrades thermally and under certain chemical conditions to yield hydrochloric acid and formaldehyde (CH2O). In solution, the latter two compounds are in equilibrium with the known potent carcinogen bis(chloromethyl)ether (BCME). A sample of commercial THPC contained from 4% (at pH 0.4) to 14% (at pH greater than 4.5) free CH2O. The material, as supplied by the manufacter, showed pH 0.4. Gas chromatographic analysis of aqueous commercial THPC did not reveal any peak chracteristic of BCME under conditions where 0.1 ppm of the material can be detected. Application to mouse skin of THPC ( 2 mg in 0.1 ml DMSO) and of Pryset TKP (7 mg in 0.1 ml DMSO), three times per week for 400 days with 20 female ICR/Ha Swiss mice per group, gave one squamous carcinoma in the THPC-treated group. THPC was inactive as an initiating agent in two-stage mouse skin carcinogenesis with phorbol myristate acetate as promoter. Both agents were active as tumor promoters, using a single application of 7,12-dimethylbenz[a]anthracene (20 microng in 0.1 ml acetone) as initiator. With THPC as promoter (2 mg in 0.1 ml DMSO, thrice weekly) 3 of 20 mice bore papillomas which progressed to squamous carcinoma. With Pyroset TKP as promoter (7 mg in 0.1 ml DMSO) 7 of 20 mice bore papillomas of which two progressed to squamous carcinoma.
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PMID:Evaluation of chemical flame retardants for carcinogenic potential. 84 2

Epidural spinal cord compression was produced in rats by injection of Walker 256 carcinoma cell suspension anterior to the T-12 or T-13 vertebral body. The tumor grows through the intervertebral foramina to compress the spinal cord and produce paraplegia in 3 to 4 weeks. The effect of several treatments upon clinical signs was assessed. Dexamethasone caused a significant but transient improvement in neurological function. Radiation therapy likewise improved neurological function, and was more effective when given by a high-dose protracted course than when given either in a single dose or a low-dose protracted course. Laminectomy was not helpful in relieving neurological symptoms. Dimethyl sulfoxide did not relieve neurological symptoms. Cyclophosphamide was most effective in relieving neurological symptoms, and most of the animals that were treated with that drug when they were severely weak but still able to move their hind limbs recovered fully. Some animals that were totally paraplegic when treatment began recovered function after radiation therapy or cyclophosphamide treatment, but recovery was better if treatment was started when animals could still move their hind limbs. This animal model appears to be a useful way of studying the treatment of human spinal cord compression produced by epidural neoplasms.
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PMID:Treatment of experimental spinal cord compression caused by extradural neoplasms. 89 41

Maturation of the intracisternal A-type particle found in two mouse plasma cell tumors was induced by treating the cells in culture with IDU-DMSO or with DMSO only. Morphologically, the mature particles with electron-dense nucleoids closely resembled the mature particles described in human tumor cell lines treated in a like manner. They also closely resembled the virus that has been described in guinea pig leukemias. It was not possible to demonstrate infectivity of the mature particle, as latent intracisternal A-type particles induced by IDU were found in the mouse cells presumed to be free of virus. The biochemical studies did not show distinct new peaks of virus-specific particles in sucrose density gradients when the particles in the treated cells were compared with the particles of the untreated cells. There was a difference in the density of the particles observed in the induced cells (1.2) and those of the control cells (1.185). This may reflect the difficulty of separating mature and immature particles. Analysis of the RNA present in the particles showed that the ratio of heavy-molecular-weight RNA in activated cells to the predominant species (21S) is much greater than that in control cells. Detectable levels of enzyme activity were not found in the induced particles. This could be due to too low a concentration of particles in the preparations.
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PMID:Studies on the intracisternal A-type particles in mouse plasma cell tumors: induction of maturation of the particles. 105 37

By oral application of TTT, disolved in concentrated DMSO, it was possible by means of a long-term experiment to produce tumors in female rats (Wistar strain). Contrary to all previous findings the tumor-inducing effect of this substance has been proved in this way for the first time.
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PMID:Tumor-inducing effect of trinitroso-trimethylene-triamine (TTT) when orally applied in dimethylsulphoxide (DMSO) for solvent. 123 94

The understanding of intermediate endpoint biomarker expression in relation to the sequential events in bladder tumorigenesis establishes a useful approach for evaluating chemopreventive agents. Biomarkers may be genotypic or phenotypic and function as biomarkers of susceptibility, exposure, effect, or disease. This paper reviews several years of research on biomarkers and their use in monitoring chemoprevention therapy. In initial animal experiments, mice were dosed with N-butyl-N-(4-hydroxybutyl)nitrosamine (OH-BBN) while co-administering N-(4-hydroxyphenyl)retinamide (4-HPR). 4-HPR did not statistically reduce tumor incidence, but did affect tumor differentiation and, consequently, nuclear size and DNA ploidy. These results suggest that nuclear size and ploidy may function as intermediate endpoint biomarkers of effect for oncogenesis and that epigenetic as well as genetic mechanisms may be primary in the oncogenic process. Early biomarkers of effect which occur prior to genetic effects or chromosome aberration may portend a higher probability of being modulated by differentiating agents such as retinoids. In vitro studies demonstrated that RPMI-7666 cells cultured with a phorbol ester tumor promoter (12-O-tetradecanoyl-phorbol-13-acetate) could be redifferentiated with 13-cis-retinoic acid and dimethyl sulfoxide (DMSO). F-actin, a cytoskeletal biomarker with a presumed function in the epigenetic mechanisms of carcinogenesis, could also be normalized in HL-60 cells treated with 4-HPR or DMSO. A clinical evaluation of F-actin in patients with varying degrees of risk confirmed the value of F-actin as a differentiating biomarker useful for bladder cancer risk assessment. The clarification of when the phenotypic changes of F-actin occur in the oncogenic process was achieved when a variety of biochemical changes were mapped in the patients with bladder cancer. These studies confirmed that G-actin, a reciprocal form of F-actin, is increased relatively early in bladder cancer oncogenesis when multiple biomarkers are quantitated in the field, adjacent area, and the tumor. Comparison of each individual biomarker's expression from field, adjacent to tumor, and tumor, and subsequent cluster analysis of these biomarkers, indicated that the possible sequence of phenotypic expression of biomarkers in bladder cancer oncogenesis is from G-actin, to p300 antigen, to epidermal growth factor receptor (EGFR), to p185 (neu oncogene product), to DNA aneuploidy and, finally, to visual morphology.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Intermediate endpoint biomarkers for chemoprevention. 130 96

Mechanistic details of the interaction of 1,10-phenanthroline and its copper complex with Ehrlich ascites tumor cells were examined, using inhibition of cell proliferation, DNA breakage, and increased membrane permeability as indices of cellular damage. The metal chelating agent, 1,10-phenanthroline (OP), the 1:0.5 complex of 1,10-phenanthroline and CuCl2 [(OP)2Cu], and CuCl2 inhibited growth of Ehrlich ascites tumor cell monolayers during 48-h treatments by 50% at about 3.5, 2, and 70 nmol/10(5) cells/mL, respectively. (OP)2Cu at 10 nmol/10(5) cells also enhanced uptake of trypan blue dye during 6 h of treatment, while dye uptake in OP- and CuCl2-treated cells remained similar to controls. DNA breakage, measured by DNA alkaline elution, was produced during 1-h treatments with (OP)2Cu at drug/cell ratios similar to those producing growth inhibition. Copper uptake was similar for both (OP)2Cu and CuCl2. Electron spin resonance (ESR) spectroscopy suggested that cellular ligands bind copper added as (OP)2Cu or CuCl2 and then undergo time-dependent reductions of Cu(II) to Cu(I) for both forms. Inhibition of (OP)2Cu-induced single-strand scission and trypan blue uptake by scavengers of activated oxygen is consistent with participation of superoxide and H2O2 in both processes. In contrast, superoxide dismutase (SOD) did not reduce the magnitude of the fraction of cellular DNA appearing in lysis fractions prior to alkaline elution of (OP)2Cu-treated cells. Dimethyl sulfoxide (DMSO) inhibited uptake of trypan blue dye but did not inhibit DNA strand scission produced by (OP)2Cu. Thus, multiple mechanisms for generation of oxidative damage occur in (OP)2Cu-treated cells. Growth inhibition produced by OP or (OP)2Cu, as well as the low levels of strand scission produced by OP, was not reversed by scavengers.
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PMID:Interactions of 1,10-phenanthroline and its copper complex with Ehrlich cells. 131 48

The interaction of 2,9-dimethyl-1,10-phenanthroline (neocuproine or NC) and its copper complex with Ehrlich ascites tumor cells was studied. NC is frequently used as a negative control in studies of in vitro DNA degradation by copper phenanthroline and has also found use as a potential inhibitor of damage from oxidative stress in biological systems. NC inhibited Ehrlich cell growth in monolayer culture over 48 h treatment by 50% at 0.05 nmol/10(5) cells. Addition of 5- to 100-fold ratios of CuCl2 to NC (at 0.035 nmol NC/10(5) cells) produced progressively more growth inhibition. Addition of 1:0.5 ratios of NC to CuCl2 over the range of NC concentrations 0.08-0.2 nmol/10(5) cells/mL resulted in DNA single-strand breakage during 1-h treatments as measured by DNA alkaline elution. Concomitant addition of catalase or dimethyl sulfoxide (DMSO) inhibited DNA strand scission, while superoxide dismutase enhanced breakage. Catalase and DMSO also inhibited induction of membrane permeability by the copper complex of NC. These cellular effects apparently result from the intracellular generation of hydroxyl radical from H2O2. NC facilitated the uptake of copper into cells, though it was initially bound as a copper-histidine-like complex. The internalized copper was reduced to Cu(I), bound mostly as (NC)2Cu(I). To explain the (NC)2Cu-dependent generation of hydroxyl radical, it is hypothesized that glutathione successfully competes for Cu(I), converting it to a redox-active form that can catalyze the reduction of molecular oxygen to .OH. Model studies support this view. Radical scavengers did not reverse growth inhibition produced by NC or NC + CuCl2.
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PMID:Oxidation-reduction reactions in Ehrlich cells treated with copper-neocuproine. 133 27


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