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)

12-O-Tetradecanoyl phorbol-13-acetate (TPA), a tumor promoter, stimulates DNA synthesis in mouse epidermal cells in vivo and in vitro. This response appears to be mediated through polyamine metabolism because ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17)activity is markedly increased shortly after promoter exposure and this induction varies in magnitude according to dose and promoter potency of a series of phorbol esters. In vitro, exogenous putrescine (0.01-10 mM) results in a dose-related increase and prolongation of promoter-stimulated DNA DNA synthesis, a phenomenon noted in other systems of polyamine-mediated growth stimulation. The anti-inflammatory steroid fluocinolone acetonide (FA), an inhibitor of tumor promotion, prevents TPA stimulation of epidermal proliferation in vivo and in vitro. In vitro, FA most effectively prevents stimulation of DNA synthesis when applied is not required. Paradoxially, FA potentiates the increase in ornithine decarboxylase activity after TPA administeration both in vivo and in vitro. Furthermore, the inhibition of TPA-stimulated DNA synthesis by FA in vitro can be reversed by exogenous putrescine. These results suggestthat FA exerts its antipromotion effect by reducing the sensitivity of the cell to polyamines or by reducing intracellular polyamine levels.
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PMID:Dissociation of tumor promoter-stimulated ornithine decarboxylase activity and DNA synthesis in mouse epidermis in vivo and in vitro by fluocinolone acetonide, a tumor-promotion inhibitor. 26 43

Dunn osteosarcomas synthesize 2 times more alkaline phosphatase than do Ridgeway osteosarcomas, 3 times more than do HeLa cells, and 4 to 5 times more than do rat or mouse fibroblast cell cultures. Implants of killed freeze-dried Dunn cell cultures into the thigh muscles are resorbed and replaced by normal cartilage, bone, and bone marrow tissue, while implants of freeze-dried Ridgeway cells are resorbed and replaced by fibrous tissue only. Outgrowths of normal muscle septum connective tissue cells onto the stroma of Ridgeway tumors differentiate into fibrous tissue. Cultures of either tumor on a substratum of bone matrix stroma prepared from normal bone proliferate, assume a spherical shape, and perpetuate the transformed osteoblast-like cell without forming attachments or adapting to the contour of the substratum. Outgrwoths of muscle mesenchymal cells on the Dunn tumor stroma differentiate into cartilage. Dunn osteosarcoma cell cultures proliferate on the inside and produce deposits of normal bone (not tumorous bone) on the outside of diffusion chambers. Killed freeze-dried cell cultures produce transfilter deposits of normal bone and bone marrow, but the quantity is significantly lower. On a substratum of cellulose acetate, outgrowths of muscle connective tissue will differentiate into cartilage when cell-free Dunn stroma is present under the organ culture grid. Tumorigenesis and normal cartilage and bone morphodifferentiation are antithetic, but tumor cells transfer a bone morphogen similar to the bone morphogenetic protein (BMP) of normal bone matrix. BMP recruits mesenchymal cells to proliferate and differentiate into cartilage and bone.
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PMID:Osteogenesis and chondrogenesis in transplants of Dunn and Ridgway osteosarcoma cell cultures. 27 82

The tumor-promoting agent 12-O-tetradecanoyl-phorbol-13-acetate (TPA) caused a 2- to 3-fold enhancement of transformation of secondary rat embryo cells that had been injected with a temperature-sensitive mutant of adenovirus type 5(H5ts 125). In addition, transformed foci appeared earlier and were larger in cultures grown in the presence of TPA. The addition of TPA could be delayed until up to 7 days after viral injection and still enhancement was observed. Exposure of the cells to 7,12-dimethylbenz[a]pyrene prior to H5ts125 infection also resulted in a 2- to 4-fold enhancement of transformation, and this enhancement was further augmented 2- to 3-fold when cells were grown in TPA after virus infection. Whereas TPA did not enhance the cloning efficiency of normal rat embryo cells, it did enhance the cloning efficiency of isolated colonies of adenovirus-transformed cells when these were grown alone or cocultured with a 100-fold excess of normal rat embryo cells. The enhancement of adenovirus transformation by TPA appears to be due to its ability to facilitate expression of the transformed state rather than an effect on virus uptake or integration.
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PMID:Interactions between adenovirus, a tumor promoter, and chemical carcinogens in transformation of rat embryo cell cultures. 27 73

Spontaneous and induced differentiation of murine erythroleukemia cells (strain 745A DS19 ) is reversibly inhibited by 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent promoter of mouse skin carcinogenesis, and by other tumor-promoting macrocyclic plant diterpenes, but it is not by nonpromoting diterpenes. Twelve clones randomly isolated from this strain vary in their response to TPA. All clones are induced to differentiate by several compounds, the most potent of which is hexamethylene bisacetamide. In six clones TPA (100 ng/ml) caused greater than 90% inhibition of differentiation, as measured by the appearance of benzidine-reactive cells. In two clones cell differentiation was not inhibited by TPA even at concentrations as high as 1 microgram/ml. In four clones, differentiation was only partially inhibited (16 to 47%) by TPA. Clones resistant to TPA inhibition of differentiation were also resistant to structurally related tumor-promoting agents. The isolation of variant cell lines, sensitive and resistant to TPA, provides a tool for elucidating the mechanism of tumor promoter-mediated inhibition of cell differentiation.
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PMID:Heterogeneity of murine erythroleukemia cells with respect to tumor promoter-mediated inhibition of cell differentiation. 27 96

The effect of the fecal stream on the induction of intestinal tumors was studied in 3 groups of SD rats. Rats in group 1 were subjected to single-barreled colostomies for the complete exclusion of the fecal stream at the proximal one-third level of the colons and were given consecutive iv injections of methylazoxymethanol acetate. Rats in group 2 were given methylazoxymethanol acetate alone. Rats in group 3 were not treated and served as controls. Tumors were noted in the small and large intestines of almost all rats in both groups 1 and 2. Even animals with single-barreled colostomies frequently developed tumors in the colon distal to the colostomy where the mucosa did not have contact with the fecal stream. These results indicated that carcinogens could probably reach the intestinal mucosa via the vascular system as well as by biliary transport.
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PMID:Effect of colostomy on intestinal carcinogenesis by methylazoxymethanol acetate in rats. 27 16

Human promyelocytic leukemia cells (HL-60) were induced to differentiate into mature cells by the tumor-promoting agent phorbol-12-myristate-13-acetate and other related phorbol diesters. Differentiation was determined by an increase in the percent of myelocytes, metamyelocytes, and other mature myeloid cells as well as by an increase in the percent of phagocytizing cells. Induction of differentiation could be determined after 2 days of treatment with phorbol-12-myristate-13-acetate at a dose as low as 6 X 10(11) M. A correlation was found between reported tumor-promoting activity of a series of phorbol esters and their ability to induce myeloid differentiation and to inhibit cell growth. It is suggested that tumor-promoting agents like chemicals that induce terminal differentiation in these cells, at extremely low concentrations, may be used as a tool in the study of the control of cell growth, cell differentiation, and malignancy in human leukemic cells.
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PMID:Induction of terminal differentiation in human promyelocytic leukemia cells by tumor-promoting agents. 28 11

Addition of a potent tumor promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA), to mouse myeloid leukemia line cells (Ml) in suspension cultures inhibited both functional and morphological differentiation of the cells induced by dexamethasone or protein inducer. A positive correlation was found between the tumor-promoting activities of several plant diterpenes and their inhibition of cell differentiation. The inhibition of cell differentiation by TPA was reversible and was unrelated to its cytotoxic action.
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PMID:Inhibition of functional and morphological differentiation of cultured mouse myeloid leukemia cells by tumor promoters. 28 66

Previous studies demonstrated that 12-O-tetradecanoyl-phorbol-13-acetate (TPA), a tumor promoter, is a potent inhibitor of inducer-mediated differentiation of murine erythroleukemia cells. Inhibition of cell differentiation was associated with inhibition of cell growth. The present studies, employing a cell line adapted for growth in TPA, demonstrate that inhibition of differentiation is not dependent upon inhibition of cell growth or a change in the cell division cycle; neither is inhibition of differentiation accompanied by detectable effect on cell uptake of [3H]hexamethylene bisacetamide, the inducer used in these studies. TPA causes an inhibition of expression of all hexamethylene bisacetamide-inducible erythroid characteristics measured, including commitment to terminal cell division, accumulation of globin mRNA, and synthesis of globins, spectrin, heme synthetic enzymes (delta-aminolevulinic acid dehydratase and uroporphyrinogen-I synthase) and heme. A hypothetical model for the inhibitory action of tumor promoters on terminal cell differentiation is discussed.
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PMID:Tumor promoter-mediated inhibition of cell differentiation: suppression of the expression of erythroid functions in murine erythroleukemia cells. 28 29

The induction of sister chromatid exchanges (SCE) in the second postirradiation mitosis was studied in mouse 10T1/2 cells irradiated with 400 rads (4 grays) and maintained in stationary growth for several hours after x-ray exposure (similar to liquid holding recovery experiments in bacterial cells). X-irradiation with no recovery period induced few SCE. With short recovery intervals, however, the SCE frequency rose in parallel with the increase in survival, reaching a maximum increase of 2-fold after 4 hr; SCE declined with longer recovery intervals. The influence of postirradiation incubation with the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) and with the protease inhibitors antipain and leupeptin was studied on spontaneous, x-ray-induced (no recovery), and recovery-induced (4 hr) SCE. TPA (0.1 microgram/ml and 1.0 microgram/ml) increased the frequency of both spontaneous and direct x-ray-induced SCE, but not of recovery-induced SCE. Incubation with the protease inhibitors suppressed both TPA- and recovery-induced SCE, but had no effect on direct x-ray-induced SCE. These results are discussed in relation to the hypothesis that promotional events in carcinogenesis may involve the expression of mutational damage in cells by mitotic segregation.
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PMID:Effect of tumor promoters, protease inhibitors, and repair processes on x-ray-induced sister chromatid exchanges in mouse cells. 28 35

12-O-Tetradecanoylphorbol-13-acetate, a potent promoter of carcinogenesis in mouse skin, enhanced differentiation of cultured mouse myeloid leukemia cells (M1) induced by human urinary protein or by lipopolysaccharide from Salmonella typhosa. 12-O-Tetradecanoylphorbol-13-acetate enhanced differentiation of all the markers tested, such as phagocytosis, Fc rosette formation, lysozyme activity, and morphological change. Other potent tumor-promoting macrocyclic plant diterpenes also enhanced the induction of differentiation, but no-tumor-promoting diterpenes did not. These findings were in marked contrast with generally accepted findings on the inhibitory effect of 12-O-tetradecanoylphorbol-13-acetate on terminal differentiation observed in other cell culture systems but consistent with the observations with some kinds of leukemia cells.
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PMID:Enhancing effect of phorbol esters on induction of differentiation of mouse myeloid leukemia cells by human urinary protein and lipopolysaccharide. 29 79


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