Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.1.17 (ornithine decarboxylase)
 6,351 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidermal hyperplasia was induced in hairless mice (hr/hr) by topical n-hexadecane treatment of tail and back skin. Following this skin irritation, a granular layer developed in interfollicular regions of the tail epidermis. An increase of ornithine decarboxylase activity, of thymidine triphosphate incorporation into DNA and of amino acid incorporation into protein was found. Shown histologically and by measurement of the called biochemical parameters, ciclosporin (cyclosporin A, CAS 59865-13-3; pretreatment with 30 mg/kg b.w. per day subcutaneously for 7 days) inhibited the development of epidermal hyperplasia in back and tail epidermis.
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PMID:Inhibition of n-hexadecane-induced epidermal hyperplasia due to systemically administered ciclosporin. 204 75

An inhibitor of ornithine decarboxylase, difluoromethylornithine (DFMO), and two inhibitors of prostaglandin biosynthesis, piroxicam and menhaden fish oil, were examined for their effect on intestinal tumorigenesis in male Sprague-Dawley rats fed a 5% fat semisynthetic diet. Each agent was given individually in one of two doses as follows: DFMO, 0.05% and 0.1% in the drinking water; piroxicam, 65 mg/kg diet and 130 mg/kg diet; and menhaden fish oil, 1.25% and 2.50% of the diet. Additional animal groups were given combinations of the lower dose of DFMO and the lower dose of either piroxicam or fish oil. Intestinal tumors were induced by sc injections of azoxymethane (AOM; CAS: 25843-45-2) at 8 mg/kg (body wt) weekly for 8 weeks. Test diets were started 1 week prior to the first dose of AOM, and the rats were sacrificed 26 weeks later. Rats that received either dose of DFMO or the high dose of piroxicam developed significantly fewer intestinal tumors compared to controls. The low dose of piroxicam and the fish oil given at either dose level had no effect. The combination of the low dose of DFMO and the low dose of piroxicam reduced tumor formation more than either dose of DFMO alone, whereas the low dose of DFMO and fish oil together was no more effective than either dose of DFMO alone. These results show that a combination of a small amount of DFMO and piroxicam, each acting through a different mechanism, exerts an additive inhibitory effect on intestinal tumor formation in rats.
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PMID:Inhibition of intestinal carcinogenesis in rats: effect of difluoromethylornithine with piroxicam or fish oil. 309 48

The hepatic levels of 5'-deoxy-5'-methylthioadenosine (MTA) were measured in the livers of adult male Sprague-Dawley rats a) killed at various times during the liver regeneration process, b) killed at times after partial hepatectomy when the liver mass had already been completely restored (hereafter called post-regeneration livers), or c) continuously fed 3'-methyl-4-dimethyl-aminoazobenzene (CAS: 55-80-1) up to the full development of hepatoma and killed at regular intervals during hepatocarcinogenesis. Hepatic MTA levels were always significantly decreased, although to different degrees in both in vivo models of hepatic growth and at all times during the investigation. Astonishingly, the MTA levels were also significantly decreased in the post-regeneration livers, in which there was also a significant increase in the activity of adenosylmethionine decarboxylase (S-adenosyl-L-methionine decarboxylase; EC 4.1.1.50) with normal levels of activity of ornithine decarboxylase (EC 4.1.1.17). These results demonstrate that a) the MTA content is always decreased in rat liver whenever this organ is involved in a proliferative process (whether controlled or uncontrolled); b) the decrease in hepatic MTA content is a biochemical feature necessary for, but by no means by itself sufficient for, hepatocyte proliferation to occur, since this decrease remains long after complete restoration of the liver mass; and c) the return of the hepatocytes to the normal biochemical program after restoration of the liver mass is not complete, even though these cells become quiescent, because there are still some biochemical abnormalities in the post-regeneration livers.
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PMID:Persistently decreased hepatic levels of 5'-deoxy-5'-methylthioadenosine during regeneration of and chemical carcinogenesis in rat liver. 345 57

The effect of various levels of polyunsaturated fat (corn oil) and saturated fat (lard) fed during the initiation stage of colon carcinogenesis was studied in male F344 rats. The animals were fed the diets containing 5, 13.6, and 23.5% corn oil or lard 2 weeks before, during, and until 1 week after sc injection of 15 mg azoxymethane [(AOM) CAS: 25843-45-2]/kg body weight, once weekly for 2 weeks (designated as initiation). One week after AOM treatment, groups of animals were transferred to their respective 5% corn oil or lard diets. Additional groups consuming 5% corn oil or lard were transferred to 23.5% corn oil or lard, respectively (post-initiation stage). All animals were fed these diets until the termination of the experiment. Fecal bile acids and colonic mucosal ornithine decarboxylase activity were measured in vehicle-treated animals fed the experimental diets for 14 weeks. Body weights and intakes of total calories, protein, nonnutritive fiber, and micronutrients were comparable among the various dietary groups. The animals fed the 23.5% corn oil diet during the postinitiation stage had a higher incidence of colon tumors than did those fed the 5% corn oil diet, whereas feeding of 23.5 and 13.6% corn oil diets during the initiation stage had no effect. In contrast, animals fed the 23.5 and 13.6% lard diet during the initiation stage and 23.5% lard diet during the postinitiation stage developed more colon adenocarcinomas than did those fed the 5% lard diet. The excretion of fecal deoxycholic acid, lithocholic acid, and 12-ketolithocholic acid and the activity of colonic mucosal ornithine decarboxylase activity were higher in animals fed the 23.5% corn oil or lard diet during the postinitiation compared to the levels in animals fed the 5% corn oil or lard diet.
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PMID:Effect of different levels of dietary corn oil and lard during the initiation phase of colon carcinogenesis in F344 rats. 346 18

The acute effects of 12-O-tetradecanoylphorbol-13-acetate [(TPA) CAS: 56937-68-9], T-2 toxin (CAS: 21259-20-1), capsaicin (CAS: 404-86-4), cigarette smoke condensate (CSC), and ethanol (CAS: 3807-77-0) were examined in secondary cultured human esophageal epithelial cells in serum-free LHC-8 medium. Effects were evaluated by morphology and measurement of clonal growth rate (population doublings per day), cross-linked envelope (CLE) formation, and the enzymatic activities of ornithine decarboxylase (ODC) and plasminogen activator (PA). All compounds tested were inhibitory to clonal growth; concentrations causing 50% growth inhibition were estimated as 10 nM TPA, 6 nM T-2 toxin, 40 microM capsaicin, 8 micrograms CSC/ml, 540 mM ethanol, and 0.8 microgram CSC/ml with 220 mM ethanol. None of the compounds tested induced CLE formation, although calcium ionophore (A23187) could induce CLE in at least 60% of the cells. TPA (10 and 100 nM) decreased the ODC activity of cells, and capsaicin (100 microM) induced ODC by 220%. TPA (1-100 nM) and capsaicin (100 microM) also induced PA activity. Slight increases in ODC activity by CSC (10 micrograms/ml), CSC (1 microgram/ml) with ethanol, and T-2 toxin (1 nM) were observed, but PA activity was not affected by these compounds. The results indicated that the response of human esophageal epithelial cells to TPA is both similar to and different from that reported for human epidermal and bronchial cells in vitro. Enhancement of PA activity and decrease in ODC by TPA are found in all three human epithelial cell types. However, these changes are not associated in esophageal cells with increased CLE formation as reported in studies with the use of bronchial and epidermal epithelial cells. The results from these acute studies provide the basis for designing in vitro carcinogenesis investigations using these agents.
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PMID:Effects of tumor promoters and cocarcinogens on growth and differentiation of cultured human esophageal epithelial cells. 346 55

This study evaluated the role of polyamines in mediating the effect of ovine prolactin (oPRL) and ovine growth hormone (oGH) on the growth of the N-nitroso-N-methylurea [(NMU) CAS:684-93-5]-induced rat (Sprague-Dawley) mammary cancer cultured in soft agar. oPRL and oGH had a dose-related growth-promoting effect when added to NMU-induced mammary tumors cultured in soft agar in the absence of serum. The effect of oPRL and oGH was blocked by alpha-difluoromethylornithine (DFMO), a suicide inhibitor of ornithine decarboxylase, the rate-limiting enzyme of polyamine biosynthesis. Exogenous administration of polyamines reversed the inhibitory effect of DFMO and completely restored the action of oPRL and oGH. Our results indicated that polyamines are essential in mediating the growth of the NMU-induced mammary tumor under these experimental conditions.
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PMID:Polyamines as mediators of the effect of prolactin and growth hormone on the growth of N-nitroso-N-methylurea-induced rat mammary tumor cultured in vitro in soft agar. 385 88

The role of polyamines as mediators of the mitogenic effect of 17 beta-estradiol (E2) was investigated in the N-nitrosomethylurea [(NMU) CAS: 684-93-5; N-methyl-N-nitrosourea]-induced Sprague-Dawley rat mammary tumor grown in the soft agar clonogenic assay under serum-free medium conditions. Inhibition of polyamine biosynthesis with alpha-difluoromethylornithine (DFMO) (1 mM), an irreversible inhibitor of ornithine decarboxylase, completely blocked the growth-promoting effect of E2 (10(-8) M) in this system. Exogenous administration of putrescine (2.5 mM), spermidine (0.1 mM), and spermine (0.1 mM) reversed the inhibitory effect of DFMO and completely restored the action of E2. These polyamines, however, had no effect on tumor growth when they were added alone in identical concentrations. The results indicate that polyamines are essential but probably not sufficient in mediating the E2 effect on the growth of the NMU-induced mammary tumor under these experimental conditions.
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PMID:Polyamines as mediators of estrogen action on the growth of experimental breast cancer in rats. 643 Nov 70

The effect of all-trans-retinoic acid (RA), an oxidative product of vitamin A, on cell growth, cell cycle kinetics, RNA content, and protein content of exponentially growing Friend erythroleukemia (FL) cells was determined and compared with the results obtained with dimethyl sulfoxide [(DMSO) CAS: 67-68-5; methyl sulfoxide], an inducer of differentiation, and alpha-difluoromethylornithine (DFMO), a potent inhibitor of ornithine decarboxylase (EC 4.1.1.17) activity. Growth inhibition of FL cells was observed only during continuous treatment with RA. While RA did not prevent growth to a high cell density, if cultures were maintained in exponential growth, cell number was reduced by 37, 67.4, and 72.2% after 6-day exposure to 10(-7), 10(-6), and 10(-5) M RA, respectively. In comparison, 280 mM (2%) DMSO and 5 mM DFMO inhibited growth over the same time course by 92 and 97.3%, respectively. DMSO resulted in an early, transient (18-24 hr) accumulation of cells in G1 phase followed by a later (5 day), irreversible accumulation of G1 cells. RA required several cell generations (48-72 hr) before a dose-dependent G1 accumulation was observed. Two populations of RA-treated FL cells could be identified: one with an intermediate RNA content (T-cells) similar to near-plateau-phase control cultures and the other with low RNA content (Q-cells) similar to that observed for DMSO-differentiated (D) cells. The kinetics of the decrease in RNA content of Q-cells paralleled those of D-cells in DMSO-treated cultures; the proportion of Q- versus T-cells in RA-treated cultures was dependent on both concentration and length of exposure. DFMO treatment did not give rise to low-RNA-containing Q-cells. Protein content of RA-treated cells was also diminished and approached that observed for hemoglobin-containing D-cells. FL cells were recoverable from long-term (greater than 5 days) treatment with RA, though 2-3 days were required for reestablishment of exponentially growing cultures; apparently only moderate RNA-containing T-cells repopulated the culture. Neither RA nor DFMO treatment gave rise to benzedine-positive, hemoglobin-containing cells as compared to DMSO that induced differentiation in these cultures.
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PMID:Effects of retinoic acid versus dimethyl sulfoxide on Friend erythroleukemia cell growth. I. Cell proliferation, RNA content, and protein content. 658 24

Ninhydrin (2,2-dihydroxy-1,3-indanedione; CAS No. 485-47-2) is widely used as a reagent for the detection of free amino and carboxyl groups in proteins and peptides. It is an irritant to mammalian skin. Various toxic effects of ninhydrin have been reported in laboratory animals; however, so far there has been no evaluation of its carcinogenic and co-carcinogenic potential in laboratory animals by long-term in vivo bioassay. Ninhydrin was found to induce the activity of gamma-glutamyl transpeptidase (GGT) in mouse skin but it failed to alter the activity of the enzyme ornithine decarboxylase when compared with animals treated with standard tumour promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA). In the present investigations, the tumour-promoting activity of ninhydrin (including both stage I and stage II of tumour promotion) was tested on Swiss albino mice in a multistage mouse skin model of carcinogenesis. The animals were initiated with a single topical application of 7,12-dimethylbenz-anthracene followed by four topical applications of ninhydrin biweekly as stage I promoter for 2 wk. Stage II promotion was twice weekly through topical application of mezerein. The results revealed that ninhydrin is a strong stage I tumour promoter and its efficacy was comparable with that of TPA at the dose level used in the experiment. However, ninhydrin failed to produce tumours when tested as a stage II or complete tumour promoter on mouse skin.
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PMID:Tumour-promoting activity of ninhydrin on mouse skin. 804 78