Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Skin tumor promotion induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) was inhibited by a concurrent and topical application of phthalic acid mono-n-butyl ester cupric salt (PAMBCu) in CD-1 mice initiated with 7,12-dimethylbenz[a]anthracene. PAMBCu inhibited TPA-caused epidermal ornithine decarboxylase (ODC) induction and ear edema formation, i.e. skin inflammation. However, neither PAMBCu nor superoxide dismutase (SOD) inhibited TPA-caused ODC induction in primary cultured mouse epidermal cells. 7-Bromomethylbenz[a]anthracene (BrMBA) is known to be a non-TPA type of tumor promoting agent. Epidermal ODC induction and inflammation caused by BrMBA were not inhibited by a concurrent application of PAMBCu. When mice were topically treated twice with PAMBCu, i.e. concurrently with and 7 h after BrMBA treatment, BrMBA-caused ODC induction was markedly suppressed. The same dose regimen of PAMBCu, however, failed to inhibit tumor promotion and inflammation caused by BrMBA. PAMBCu showed SOD-mimetic activity in superoxide generating systems, i.e. xanthine-xanthine oxidase reaction and TPA-stimulated polymorphonuclear leukocytes (PMN). Mono-n-butyl phthalate, which lacks SOD-mimetic activity, failed to inhibit TPA-caused ODC induction and skin inflammation. Therefore, inhibition by PAMBCu of TPA-caused tumor promotion, epidermal ODC induction and inflammation may be attributable to its SOD-mimetic activity. The results also support the contention that a superoxide anion of non-epidermal cell origin, such as PMN and macrophages, plays a role (probably some enhancing role) in in vivo ODC induction and tumor promotion caused by TPA. Failure of PAMBCu to inhibit BrMBA-caused tumor promotion suggests that superoxide anion generation is not involved in the tumor promoting action of this agent and that the anti-tumor promoting action of PAMBCu is dependent on the nature of the tumor promoting agents.
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PMID:Anti-tumor promoting action of phthalic acid mono-n-butyl ester cupric salt, a biomimetic superoxide dismutase. 211 May 12

Neoxanthin, a major carotenoid pigment of spinach, is found in the Chloroplast membrane and has an unknown function in plants. Neoxanthin inhibited the production of superoxide anions in an artificial xanthine and xanthine oxidase system and depressed DNA synthesis in methylcholanthrene (MCA)-initiated C3H10T1/2 fibroblasts. in two-stage carcinogenesis experiments, neoxanthin at 0.2 micrograms/0.2 ml inhibited the formation of tumors that were induced sequentially by 7,12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) in the buccal pouch of Syrian Golden hamsters. To assess the ongoing process of carcinogenesis, the activity of ornithine decarboxylase (ODC), required for cell proliferation, was analyzed. Neoxanthin inhibited the activity of ODC when animals were treated with neoxanthin one hour before the application of TPA in two-stage carcinogenesis. However, neoxanthin did not inhibit ODC activity when animals were treated with neoxanthin one hour before the application of DMBA in two-stage carcinogenesis, and there was no subsequent tumor formation. In a short-term anti-initiation experiment, neoxanthin inhibited the covalent binding of isotope-labeled DMBA to DNA by 53%. These results indicate that neoxanthin inhibits the initiation stage and the promotion stage in two-stage carcinogenesis. This suggests that neoxanthin may act as a potential chemopreventive agent.
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PMID:The inhibition of DMBA-induced carcinogenesis by neoxanthin in hamster buccal pouch. 861 51

In this communication, we report that iron overload augments benzoyl peroxide (BPO)-mediated tumor promotion in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mouse skin. Female albino Swiss mice were overloaded with iron and tumors were initiated by applying a single topical application of DMBA. A week after the initiation, promoting agent, BPO, was applied three times/week for 46 weeks. The appearance of the first tumor (papilloma) and the number of tumors/mouse were recorded. When compared to the control group, the iron-overloaded mice showed an increased incidence of tumors at various time intervals. In iron-overloaded animals, tumors appeared earlier and also the number of tumors/mouse was significantly higher. These data could be correlated with the iron levels of mouse skin in the two groups. Further, BPO-mediated induction in ornithine decarboxylase (ODC) activity and [3H]thymidine incorporation in cutaneous DNA were higher in the iron overload group. In addition, in iron-overloaded mice, cutaneous lipid peroxidation (LPO) and xanthine oxidase (XOD) activities were higher, whereas catalase activity was reduced. Similar to papilloma induction, a significant increase in carcinoma yield and incidence was observed in iron-overloaded animals. Based on this study, we propose that iron overload significantly increases the tumor promotion and progression potential of BPO. We suggest that oxidative stress generated by iron overload is responsible for the augmentation of BPO-mediated cutaneous tumorigenesis.
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PMID:Effect of iron overload on the benzoyl peroxide-mediated tumor promotion in mouse skin. 958 58

This study is an in vitro part of the ongoing biomarker studies with population from a polluted region of Northern Bohemia and coke-oven workers from Czech and Slovak Republics. The aim of this study is to compare DNA adduct forming ability of chemical compound classes from both the urban and coke-oven extractable organic mass (EOM) of airborne particles. The crude extracts were fractionated into seven fractions by acid-base partitioning and silica gel column chromatography. In in vitro acellular assays we used calf thymus DNA (CT DNA) with oxidative (+S9) and reductive activation mediated by xanthine oxidase (+XO) under anaerobic conditions. Both the butanol and nuclease P1 versions of 32P-postlabeling for detection of bulky aromatic and/or hydrophobic adducts were used. The results showed that the spectra of major DNA adducts resulting from both the in vitro assays are within the fractions similar for both the urban and coke-oven samples. The highest DNA adduct levels with S9-activation were detected for the neutral aromatic fraction, followed by slightly polar and acidic fractions for both samples. With XO-mediated metabolism, the highest DNA adduct levels were detected for both the acidic fractions. Assuming additivity of compound activities, then the acidic fraction, which in the urban sample comprises a major portion of EOM mass (28%), may contain the greatest activity in both in vitro assays (39 and 69%, +S9 and +XO, respectively). In contrast, the aromatic fraction constituting only 8% of total urban EOM mass may account for comparable activity (34%) with organic acids. The highest DNA adduct forming activity of the coke-oven sample accounts for the aromatic fraction (82 and 63%, +S9 and +XO, respectively) that also contains the greatest portion of the total EOM (48%). To characterize some of the specific DNA adducts formed, we coupled TLC on 20x20 cm plates with HPLC analysis of 32P-postlabeled adducts. In both S9-treated samples of the aromatic fraction, we tentatively identified DNA adducts presumably diolepoxide-derived from: 9-hydroxy-benzo[a]pyrene (9-OH-B[a]P), benzo[a]pyrene-r-7,t-8-dihydrodiol-t-9,10-epoxide[+/-] (anti-BPDE), benzo[b,j,k]fluoranthenes (B[b]F, B[j]F, B[k]F), chrysene (CHRY), benz[a]-anthracene (B[a]A) and indeno[cd]pyrene (I[cd]P). These DNA adducts accounted for about 57% of total DNA adducts detected in both S9-treated samples of the aromatic fraction. DNA adducts of XO-treated samples were sensitive to nuclease P1 and HPLC profiles of the major adducts were markedly different from the major adducts of S9-treated samples. However, the combination of TLC and HPLC did not confirm the presence of DNA adducts derived from 1-nitropyrene (1 NP), 9-nitroanthracene (9 NA) and 3-nitrofluoranthene (3 NF) that were detected by GC-MS in the slightly polar fraction. We concluded that the chemical fractionation procedure facilitates the assessing of DNA adduct forming ability of different chemical compound classes. However, based on the results obtained with the whole extracts, it does not fulfil a task of the actual contribution of individual fractions within the activity of the whole extracts. Our results are the first in detecting of DNA adducts derived from urban air and coke-oven particulate matter.
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PMID:Genotoxicity of coke-oven and urban air particulate matter in in vitro acellular assays coupled with 32P-postlabeling and HPLC analysis of DNA adducts. 963 May 30

Iron overload is known to occur in West European and American populations due to the consumption of an iron-rich diet. There are also genetic disorders which lead to body iron overload. It has been shown that iron overload predisposes humans to an increased risk of cancer. In experimental animals, iron overload is known to enhance intestinal, colon, hepatic, pulmonary and mammary carcinogenesis. However, the mechanism by which iron overload enhances chemically-induced carcinogenesis is not known. In this study, we show that iron overload acts as a mild tumor promoter in mouse skin. Female albino swiss mice were given 1 mg iron/mouse parenterally for 2 weeks to induce iron overload. These animals showed a three-fold increase in cutaneous iron concentration as compared to normal mice. Tumors were initiated by topically applying 7,12-dimethylbenz(a)anthracene (DMBA). Appearance of the first tumor (latency period), percent tumor incidence and number of tumors/mouse were recorded. When compared to the control group, iron overload mice showed an increased incidence of tumors, from 25%-55% by week 20, and tumors appeared 4 weeks earlier. The number of tumors per mouse was four-fold higher in the iron overload group. The induction of cutaneous ornithine decarboxylase (ODC) activity and [3H]thymidine incorporation in cutaneous DNA were higher in iron overload groups as compared to normal control animals. Similar to other oxidant tumor promoters, iron overload enhanced cutaneous lipid peroxidation and xanthine oxidase activity and decreased catalase activity. Our results indicate that iron overload exerts a mild tumor promoting activity in mouse skin. Our data also show that oxidative stress generated by iron overload plays an important role in the augmentation of cutaneous tumorigenesis. These data may also have implications for the enhanced risk of cancer-induction following UVB exposure of human populations with iron overload.
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PMID:Evidence that iron-overload promotes 7,12-dimethylbenz(a)anthracene- induced skin tumorigenesis in mice. 975 29

Since reactive oxygen radicals play an important role in carcinogenesis and other human disease states, antioxidants present in consumable fruits, vegetables, and beverages have received considerable attention as cancer chemopreventive agents. Thus, in order to identify antioxidants in plant extracts, test materials were assessed for potential to scavenge stable 1,2-diphenyl-2-picrylhydrazyl (DPPH) free radicals, reduce TPA-induced free radical formation in cultured HL-60 human leukemia cells, and inhibit responses observed with a xanthine/xanthine oxidase assay system. Approximately 700 plant extracts were evaluated, and 28 were found to be active in the DPPH free radical scavenging assay. Based on secondary analyses performed to assess inhibition of 7,12-dimethylbenz(a)anthracene-induced preneoplastic lesion formation with a mouse mammary organ culture model, Chorizanthe diffusa Benth. (Polygonaceae), Mezoneuron cucullatum Roxb. (Leguminosae), Cerbera manghas L. (Apocynaceae) and Daphniphyllum calycinum Benth. (Daphniphyllaceae) were selected and subjected to bioassay-guided fractionation. 5,7,3',5'-Tetrahydroxy-8,4'-dimethoxyflavonol, 5,8,4'-trihydroxy-7,3'-dimethoxyflavonol, 5,3',4'-trihydroxy-7-methoxyflavonol, and 6,3',4'-trihydroxy-7-methoxyflavonol were identified as active principles from C. diffusa. Piceatannol, trans-resveratrol, apigenin and scirpusin A were found as the active principles of M. cucullatum, olivil, (-)-carinol, and (+)-cycloolivil were active principles from C. manghas, and 5,6,7,4'-tetrahydroxyflavone 3-O-rutinoside and kaempferol 3-O-neohesperidoside were active principles from D. calycinum. Of these substances, the hydroxystilbenes piceatannol and transresveratrol have thus far been shown to inhibit carcinogen-induced preneoplastic lesion formation in the mouse mammary gland organ culture model.
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PMID:Evaluation of the antioxidant potential of natural products. 1049 28

Heat treatment of Panax ginseng C.A. Meyer at a temperature higher than that applied to the conventional preparation of red ginseng yielded a mixture of saponins with potent antioxidative properties. Thus, the methanol extract of heat-processed neoginseng (designated as 'NGMe') attenuated lipid peroxidation in rat brain homogenates induced by ferric ion or ferric ion plus ascorbic acid. Furthermore, the extract protected against strand scission in phiX174 supercoiled DNA induced by UV photolysis of H2O2, and was also capable of scavenging superoxide generated by xanthine-xanthine oxidase or by 12-O-tetradecanoylphorbol-13-acetate (TPA) in differentiated human promyelocytic leukemia (HL-60) cells. Topical application of NGMe onto shaven backs of female ICR mice 10 min prior to TPA, significantly ameliorated skin papillomagenesis initiated by 7,12-dimethylbenz[a]anthracene. Moreover, TPA-induced enhancement of epidermal ornithine decarboxylase (ODC) activity and ODC mRNA expression was abolished by a topical dose (0.68 mg) of NGMe. Likewise, TPA-induced production of tumor necrosis factor- in mouse skin was inhibited by NGMe pretreatment.
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PMID:Antioxidant and anti-tumor promoting activities of the methanol extract of heat-processed ginseng. 1075 85

A modifying effect of potential DNA intercalators, belonging to a group of carbazole, acridine and anthracene derivatives, on the course of luminol-dependent chemiluminescence of neutrophils (polymorphonuclear leucocytes; PMNL) in the process of phagocytosis was studied. This effect was also examined in reactive-oxygen-species-generating non-cellular reaction systems consisted of myeloperoxidase or xanthine oxidase. Adriamycin (Doxorubicin), which is widely applied to neoplasm therapy, was used as a reference intercalator in the conducted experiments. It was demonstrated that some structurally different derivatives of carbazole inhibited the light emission from N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced neutrophils to the same degree as adriamycin. It can be suggested that the same inhibitory effect was caused by either a different cellular distribution of the derivatives or different interactions of the derivatives with reactive oxygen species in the investigated systems. Measurements of chemiluminescence suggested that the thiol group in one of the carbazole derivatives could strongly interfere with oxidative cell metabolism. In contrast to the analogous derivative of carbazole, both anthracene and acridine derivatives, possessing an N-1'-hydroxyethyl-ethylenodiamino group, induced different increases in chemiluminescence accompanying the process of neutrophil phagocytosis. Cytotoxicity of the investigated derivatives, being tested previously in cancer cells with a sulphorhodamine B assay, was found to possess a specific representation in the complex picture of the derivative-caused modification both of neutrophil and enzymatic non-cellular chemiluminescence. We suggest that chemiluminescence assays may serve as a helpful tool in the primary screening of drug cytotoxicity.
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PMID:Cytotoxicity of some potential DNA intercalators (carbazole, acridine and anthracene derivatives) evaluated through neutrophil chemiluminescence. 1094 5

The synthesis of novel aquayamycin-derived angucycline antibiotics 13a-d has been achieved. Glycosylation of aquayamycin (6) using 2-selenoglycosyl acetate 7 as glycosyl donor proceeded in excellent yield but attempts to reductively remove the selenyl group led to rearrangement or further aromatization of the aglycon. As a consequence of these results, it became possible to prepare urdamycinone B (10) starting from aquayamycin (6). In addition, silyl protected D-olivals 12a,b were attached to the C-glycoside domain of aquayamycin (6) under protic conditions. As expected, the hydroxy and phenol groups of the benz[a]anthracene framework of 6 did not react under the glycosylation conditions employed. Stepwise removal of the silyl protecting group starting with tetrabutyl ammonium fluoride followed by use of the HF/pyridine complex suppressed a possible rearrangement of the aglycon and successfully terminated the sequence. The new angucycline-antibiotics 13a and 13b are some of the most potent xanthine oxidase inhibitors known and show cytotoxic activity with ED50-values in the range of 12.6-2.9x 10(-6) M.
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PMID:Syntheses and biological evaluation of new glyco-modified angucyclin-antibiotics. 1102 47

Vitis vinifera (grapes) is used as a fruit worldwide and known for its pharmacological properties. The present paper assesses the chemopreventive potential of Vitis vinifera against 12-O-tetradecanoyl-13-phorbol acetate (TPA)-mediated tumor promotion in 7,12-dimethyl-benz[a]anthracene (DMBA) initiated mice skin. Skin tumor initiation was achieved by a single topical application of DMBA (40 microg/animal/0.20 ml acetone) to mice. Two weeks after the initiation, promoting agent, TPA (5.0 microg/animal/0.2 ml acetone) was applied two times a week for 20 weeks. Pretreatment of Vitis vinifera 1h prior to each application of TPA resulted in protection against cutaneous tumorigenesis in dose-dependent manner. This inhibition was evident when tumor data was considered as the percentage of mice with tumor and the number of tumors per mouse. We have shown that typical application of Vitis vinifera prior to that of TPA resulted in significant inhibition against TPA-caused induction of epidermal ODC activity (P<0.001) and DNA synthesis. Application of Vitis vinifera at a dose level of 5.0 mg and 10.0 mg kg(-1) body weight in acetone prior to that of TPA treatment resulted in partial significant inhibition of oxidative stress in dose-dependent manner. The concomitant increase in the microsomal lipid peroxidation and xanthine oxidase activities were significantly reduced (P<0.001). In addition, the depleted level of glutathione and inhibited activities of antioxidant enzymes were recovered to the partial significant level. Hence, it can be suggested that Vitis vinifera can be used as a chemopreventive agent against oxidative stress and carcinogenesis.
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PMID:Chemopreventive effect of Vitis vinifera extract on 12-O-tetradecanoyl-13-phorbol acetate-induced cutaneous oxidative stress and tumor promotion in murine skin. 1245 31


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