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

To gain insight into the gene regulation and signal transduction effects of active oxygen in tumour promotion and progression, we studied the effect of active oxygen generated extracellularly by xanthine/xanthine oxidase (X/XO) in promotion-insensitive (P-), promotion-sensitive (P+) and transformed (Tx) mouse epidermal JB6 cells. Active oxygen inhibited growth, particularly of P- cells and increased poly ADPR transferase activity and PKC activity more significantly in P- cells. No phenotypic differences in the distribution pattern of PKC isotypes alpha, beta and gamma were seen in JB6 cells. PKC alpha was expressed abundantly, whereas beta and gamma were not detected. Basal levels of the antioxidant enzymes catalase and CuZn. Superoxide dismutase were higher in P+ and Tx cells. X/XO resulted in an initial decrease in the activity of these enzymes, followed by recovery or transient induction in Tx and P+ cells. X/XO induced c-myc and c-fos expression in JB6 cells, with c-fos induction being more pronounced in P- cells, whereas a biphasic increase in c-jun was seen in P+ cells. These early genes may play a role in proliferation whereas post-translational poly ADP-ribosylation and, perhaps, phosphorylation suggest a genetic-epigenetic mechanism in oxidant tumour promotion and progression.
Int J Cancer 1995 Jul 04
PMID:The effect of active oxygen generated by xanthine/xanthine oxidase on genes and signal transduction in mouse epidermal JB6 cells. 760 57

With the use of numerous drugs in the treatment of cancer, the potential for drug interactions is considerable. Because of the limited therapeutic indices of anticancer drugs, one should be aware that even small alterations in pharmacokinetics or pharmacodynamics may result in serious adverse effects. Pharmacokinetic drug interactions may alter absorption, bioavailability, distribution, metabolism and elimination patterns. For example, allopurinol inhibits the enzyme xanthine oxidase, thereby blocking the first-pass metabolism of mercaptopurine. Due to this drug interaction, plasma concentrations of mercaptopurine can increase up to 5-fold. Pharmacodynamic drug interactions are characterised by a similar or opposing pharmacological effect of both drugs upon the same biological system. For example, cotrimoxazole (trimethoprim-sulfamethoxazole) inhibits folic acid metabolism through direct binding to dihydrofolate reductase, an enzyme which is also inhibited by methotrexate. More pharmacological investigations are needed to understand the mechanisms and clinical implications of drug interactions with antineoplastic agents.
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PMID:Antineoplastic agents. Drug interactions of clinical significance. 761 29

The antitumor effect of oxygen radicals produced by hypoxanthine and xanthine oxidase reaction was studied in an experimental rabbit model. VX2 carcinomas were transplanted into rabbit hind legs. Hypoxanthine was administered continuously through the ear vein, while xanthine oxidase was administered simultaneously through the femoral artery. As a result, hypoxanthine and xanthine oxidase reacted only in the hind leg, and superoxide was produced in that area. The volume of the VX2 carcinoma was measured immediately prior to treatment and 7 days later. As an index of lipid peroxidation, thiobarbituric acid-reactive substances in the tumor tissue were measured 60 min following infusion of hypoxanthine and xanthine oxidase. Tumor growth was suppressed significantly by the hypoxanthine-xanthine oxidase reaction, and thiobarbituric acid-reactive substances in the tumor tissue infused with hypoxanthine and xanthine oxidase were significantly increased. In addition, the antitumor effect of the hypoxanthine and xanthine oxidase reaction was significantly inhibited by the administration of superoxide dismutase and catalase. Pathological examination showed that oxygen radicals produced by hypoxanthine and xanthine oxidase reaction were selectively more destructive for VX2 carcinoma tissue than muscle tissue surrounding the tumor region. These results suggest that oxygen radicals produced by hypoxanthine and xanthine oxidase reaction produce an anticancer effect and that the VX2 carcinoma used in this study was more sensitive to oxygen radicals than normal muscle tissue.
Cancer Res 1995 Apr 15
PMID:A novel cancer therapy based on oxygen radicals. 771 62

DNA damage caused indirectly via reactive oxygen species generated during reductive activation of mitomycin C was evaluated. This oxidative DNA damage was measured by determining the formation of 8-hydroxyguanine in DNA exposed to chemically or enzymatically activated mitomycin C. The level of 8-hydroxyguanine was measured indirectly by determining formamidopyrimidine-DNA glycosylase-sensitive sites induced in plasmid DNA exposed to mitomycin C and directly by a 32P-postlabeling assay for the modified base. Activation of mitomycin C by sodium borohydride in air, by H2/Pt, or xanthine oxidase in N2 caused increases in the level of 8-hydroxyguanine. The extent of the increase varied according to the incubation conditions with the greatest increase being observed in DNA exposed to mitomycin C activated under hypoxic conditions. These results support a possible indirect mechanism for DNA damage caused by mitomycin C that is mediated by reactive oxygen species.
Cancer Biochem Biophys 1994 Oct
PMID:Formation of 8-hydroxyguanine in DNA during mitomycin C activation. 772 39

Asbestos fibers cause dose-dependent, persistent increases in mRNA levels of c-jun and c-fos proto-oncogenes in rat pleural mesothelial (RPM) cells, the progenitor cells of asbestos-induced mesothelioma (N. Heintz, Y. M. W. Janssen, and B. T. Mossman. Proc. Natl. Acad. Sci. USA, 90: 3299-3303, 1993). Here we report that addition of N-acetyl-L-cysteine decreases asbestos-mediated induction of c-fos and c-jun mRNA levels in a dose-dependent fashion. Exposure of RPM cells to asbestos causes depletion of total cellular glutathione, a response that can be abolished by pretreatment with N-acetyl-L-cysteine. Pretreatment of cells with buthionine sulfoximine, an agent which diminishes glutathione pools, increases the magnitude of induction of c-fos and c-jun mRNA by asbestos. To determine whether asbestos-induced effects on proto-oncogene expression could be attributed to extracellular generation of active oxygen species (AOS), RPM cells were exposed to H2O2 or xanthine and xanthine oxidase, a generating system of AOS. These oxidant stresses did not decrease cellular glutathione levels nor alter mRNA levels of c-fos or c-jun. However, increased mRNA levels of manganese-containing superoxide dismutase and heme oxygenase were observed, indicating that RPM cells respond to AOS by increased expression of genes encoding antioxidant enzymes. These data indicate that the signaling pathways leading to c-fos/c-jun proto-oncogene induction by asbestos are not triggered directly by formation of extracellular AOS. However, intracellular thiol levels appear to influence the expression of c-fos and c-jun, suggesting a redox-sensitive component in the signaling cascade which modulates gene expression of c-fos and c-jun by asbestos.
Cancer Res 1995 May 15
PMID:Induction of c-fos and c-jun proto-oncogene expression by asbestos is ameliorated by N-acetyl-L-cysteine in mesothelial cells. 774 7

Caffeine is increasingly used as a biochemical probe for liver function, in cancer epidemiology, and in pharmacogenetics, with its recognized ability to assess the activities of CYP1A2, xanthine oxidase, and N-acetyltransferase-2. The activity of these hepatic enzymes was tested in 45 Shona children from a rural area of Zimbabwe with use of caffeine as a probe. Many of these rural black children had lower indexes of CYP1A2 activity than otherwise on our extensive records; the average value (3.78 +/- 2.9) was significantly (p < 0.001) lower than that of healthy white urban children from Zimbabwe (8.86 +/- 3.36) or from Canada (7.92 +/- 1.88), or that of healthy Canadian adults (5.96 +/- 2.4). A higher CYP1A2 activity in children than in adults is usual. The low CYP1A2 activity of the children from rural Zimbabwe calls for medical studies and suggests a widespread and perhaps serious impairment of certain liver functions. Causes could be parasitic infections with Schistosoma mansoni, causing schistosomiasis, which are endemic, in addition to generally poor nutrition and frequent iodine deficiency. By contrast, the xanthine oxidase activity in rural Shona children was slightly higher than that reported for a healthy Canadian adult population. The N-acetyltransferase activities were comparable in both the rural and urban children and were also similar to those reported in a population study of healthy adult Canadians.
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PMID:Low CYP1A2 activity in rural Shona children of Zimbabwe. 782 78

Many anticancer drugs have been shown to produce superoxide anion (O2.-) and seem to involve O2.- in their mode of action. Ionizing radiation provokes the decomposition reaction of water, producing a variety of reactive oxygen species, including O2.-. The finding that cancer cells are generally low in SOD activity may offer a theoretical base for radiation therapy and chemotherapy. The purpose of this study was to examine the protective effect of intracellular SOD against cytotoxicity induced by O2.- or radiation and to investigate whether exogenous SOD can protect cells from O2.-(-) and radiation-induced cytotoxicity. For this purpose, xanthine (X) and xanthine oxidase (XOD) were employed as an O2.- (-)generating system, and a linear accelerator was used for ionizing radiation. Cytotoxicity against monolayer cancer cell lines and leukemic cell lines was estimated by measuring the release of lactate dehydrogenase from these cells. The results revealed that the resistibilites to X- and XOD-generated O2.- and radiation correlated with intracellular Cu. Zn-SOD levels and that exogenous SOD could only slightly reduce X- and XOD-induced cytotoxicity while having no influence on radiation-induced cytotoxicity. Thus, intracellular SOD may play a central role in protecting cancer cells against reactive oxygen species generated by anticancer drugs and radiation.
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PMID:Role of intracellular SOD in protecting human leukemic and cancer cells against superoxide and radiation. 783 45

Activities of adenosine deaminase (ADA), 5'nucleotidase (5NT), xanthine oxidase (XO), superoxide dismutase (SOD), and catalase (CAT) enzymes were measured in cancerous and cancer-free adjacent bladder tissues from 36 patients with bladder cancer and in control bladder tissues from 9 noncancer patients. Increased ADA and decreased XO, SOD, and CAT activities were found in cancerous bladder tissues compared with those of cancer-free adjacent tissues and of control bladder tissues. Differences were also found between enzyme activities in the bladder of different disease stages and grades. In the cancerous tissues, only positive intracorrelations were found, but in the cancer-free adjacent tissues and control tissues, both positive and negative correlations were established between enzyme activities. Results suggested that purine metabolism and salvage pathway activity of purine nucleotides were accelerated in the cancerous human bladder tissues via increased ADA and decreased XO activities, probably together with changes in some other related enzyme activities and, free radical metabolising-enzyme activities were depressed in cancerous bladder tissues, which indicated exposure of cancerous tissues to more radicalic stress.
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PMID:Adenosine deaminase, 5'nucleotidase, xanthine oxidase, superoxide dismutase, and catalase activities in cancerous and noncancerous human bladder tissues. 807 Jun 87

The presence of cancer induces metabolic alterations in distant, tumor-free tissues and organs of the host. A remote humoral effect of cancer growing extrahepatically is an increase in the activity of oxidant and a decrease of antioxidant enzymes in the liver of the tumor-bearing animal. We speculated that TNF-alpha, produced by host cells, the cancer, or both, is responsible for these changes. When human recombinant TNF-alpha, 100 micrograms/kg/d i.p. for 5 days, was injected in groups of rats fed ad libitum, starved, or pair-fed, a decrease in the activity of superoxide dismutase and glutathione peroxidase and an increase in xanthine oxidase was observed, particularly with pair-fed controls. It is concluded that TNF-alpha, directly or indirectly, causes these enzyme alterations in the tumor-free liver of a tumor-bearing host.
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PMID:TNF-alpha effect on oxygen free radical scavenging and generating enzymes in rat liver. 808 Dec 9

Adenosine deaminase (ADA), 5'-Nucleotidase (5NT), Xanthine oxidase (XO), Cu-Zn Superoxide dismutase (SOD) and Catalase (CAT) activities were determined in gastric juices from patients with gastric cancer, ulcer, gastritis and from healthy subjects. Enzyme activities were given as units per ml gastric juice and units per mg protein in gastric juice. ADA, 5NT and XO activities were found lower and protein concentrations were found higher in the cancer group than controls. There was however no significant difference between Cu-Zn SOD activities of the cancer and control groups. In all groups including control one, we could not find catalase activities in most of the samples. On the other hand, ADA, 5NT activities and protein concentrations in the gastric juice were lower in the gastritis group than control group. In the ulcer group, we found higher Cu-Zn SOD and XO activities and lower 5NT activity and protein concentrations compared with control values. In an attempt to establish statistical correlations between mean enzyme activities, pH and protein concentrations in the gastric juices of the groups, we found noticeable intra and inter-correlations, which indicated possible relations between DNA and free radical metabolizing enzymes.
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PMID:Adenosine deaminase, 5'-nucleotidase, xanthine oxidase, superoxide dismutase, and catalase activities in gastric juices from patients with gastric cancer, ulcer, and atrophic gastritis. 814 35


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