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)

Although it has long been known that energy restriction (ER) inhibits tumors and retards aging in rats and mice, its mode of action remains unknown. In rodents, ER alters the rate of age-related changes in physiological indices. Thus, it affects a broad array of age-sensitive parameters. However, present evidence does not indicate which parameters are primary contributors to the deceleration of aging. Compared to fasting or short-term underfeeding, little is known about the metabolic effects of long-term, life-prolonging ER. We thus investigated the effects of ER on hepatic enzyme activities, including drug-metabolizing enzymes and antioxidant enzymes such as superoxide dismutase and catalase. The catalase activity was found to be higher in ER mice than in control mice both at 12 and 24 months of age. In accord with the high catalase activity, lipid peroxidation in liver was much less in ER mice than in age matched control mice. beta-Naphthoflavone, known to induce P-450 related enzymes and xanthine oxidase, was given (ip) to increase lipid peroxidation. The ER was found to inhibit lipid peroxidation after beta-naphthoflavone treatment. It was, therefore, concluded that long-term life-prolonging ER increases antioxidant defence, supporting indirectly the free radical theory of aging. It is well known that ER delays puberty in rodents and has a profound influence on serum hormone levels, including those of prolactin (PRL) and thyroid hormones. However, it remains unknown how these effects are produced by ER. We therefore investigated the effects of ER on the islets of Langerhans in the pancreas and on the pituitary-ovarian axis. In the islets of Langerhans, ER was found to increase the density of alpha-cells significantly both in 11- and 67-week-old mice. In the pituitary gland in ER mice, the cellular density of PRL-producing cells diminished significantly while that of growth-hormone-producing cells did not. One of the modes of action of ER on the endocrine system is thus concluded to be mediated by changing cellular population. Since ER decreased PRL-producing cells and PRL plays a key role in mammary tumorigenesis, we investigated whether ER decreased the gene expression of mouse mammary tumor virus (MMTV) in SHN/C3H mice. The SHN strain, which was found to have a new MMTV provirus locus, mtv-4, was used in the study.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[On the mechanisms of retardation of aging and inhibition of mammary tumorigenesis by energy restriction in SHN/C3H F1 female mice]. 174 5

We have shown, in a preliminary report, that macrophages can induce strand breaks in the DNA of co-cultured tumor cells (Chong et al., 1988). The present study is designed to determine if oxygen-centered species generated by the cell-free enzyme-substrate combination of hypoxanthine and xanthine oxidase can induce similar lesions and to identify the specific mediator(s). We report that co-incubation of murine mammary tumor cell lines with hypoxanthine and xanthine oxidase leads to the induction of DNA-strand breaks as determined by fluorescence analysis of DNA unwinding (FADU) assay or alkaline elution techniques. This damage is preventable by catalase which removes hydrogen peroxide but no protection is provided by agents to remove or prevent the formation of superoxide anion (superoxide dismutase), or hydroxyl radical (mannitol or the iron chelator o-phenanthroline). Likewise, cyclooxygenase or lipoxygenase inhibitors of arachidonate metabolism (indomethacin, nordihydroguaiaretic acid, caffeic acid) or bromophenacyl bromide do not alter the degree of DNA scission. Treatment with higher doses of oxygen species leads to significant toxicity as determined by evaluation of cell growth potential or colony-forming ability. Again, toxicity is prevented only by the presence of catalase. Tumor cells are able to rejoin strand breaks at lower, less toxic doses. When comparing different tumor cell subpopulations at various stages of progression, i.e., metastatic vs. nonmetastatic, for sensitivity to hydrogen peroxide-induced strand breakage, we found that at lower concentrations (less than 5 microM) metastatic populations are sensitive whereas nonmetastatic populations exhibit no significant breakage. At higher concentrations of hydrogen peroxide, all lines were sensitive, suggesting that a lower threshold of sensitivity may exist for more progressed tumor cell lines.
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PMID:Reactive oxygen-mediated damage to murine mammary tumor cells. 255 50

The effects of molybdenum (Mo) supplementation in the drinking water at the levels of 0.1, 0.5, 1.0, 2.0, 5.0 and 10.0 mg/l on the hepatic trace element concentrations and enzyme activities of female Sprague-Dawley rats were studied. The mean hepatic Mo concentration increased significantly in the rats supplemented with 0.1 mg Mo/l as compared to the nonsupplemented rats, but a further significant increase did not occur until the supplementation level reached 5-10 mg Mo/l drinking water. Hepatic copper concentration of the group given 0.1 mg Mo/l and hepatic iron content of the groups given 0.1 or 0.5 mg Mo/l were significantly higher than those of the other groups. The hepatic xanthine dehydrogenase/oxidase activity was not significantly affected by Mo supplementation. The hepatic sulfite oxidase (SOX) activity of the group given 0.1 mg Mo/l was significantly higher than that of the nonsupplemented group. The SOX activities of all the other supplemented groups were at a significantly different level intermediate between the first two. The hepatic superoxide dismutase (SOD) activity was significantly higher in the group given 0.1 mg/l than in the other groups. These results indicated that molybdenum enzymes and SOD might not be participants in previously reported anticarcinogenic activity of Mo, as supplementation at the level of 0.1 mg/l had been observed to be inefficacious in inhibiting N-nitrosomethylurea-induced mammary tumor incidence.
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PMID:Effect of molybdenum supplementation on hepatic trace elements and enzymes of female rats. 291 95

We have postulated that murine mammary tumor progression is fueled, in part, by tumor-associated macrophages that deliver sub-lethal oxidative stress to tumor cells. In the present study, we determined whether oxidative stress would affect murine mammary tumor cell attachment to laminin and fibronectin, critical functions in the metastatic process. Sublethal oxidative stress generated by exposure of cells to hydrogen peroxide (H2O2, 1-1000 microM/L) inhibited tumor cell attachment to immobilized laminin or fibronectin. This oxidant effect was blocked in the presence of catalase which removes H2O2. The inhibitory effect on attachment was rapid, with significant inhibition occurring at 5 min; total inhibition was achieved at 60 min with 1 mM H2O2. The oxidative stress effect was partially reversible at 20 h post-treatment and occurred at concentrations of H2O2 that do not adversely affect cell viability or growth. Pretreatment of tumor cells with H2O2 or hypoxanthanine and xanthine oxidase (to generate superoxide radical and H2O2) prior to intravenous injection, enhanced experimental lung tumor colony formation. The enhancement of experimental metastatic potential with enzyme-generated oxidative stress was completely reversed by catalase; the H2O2-mediated enhancement was only partially reversed with catalase. Thus, treatments that inhibit tumor cell attachment to extracellular matrix proteins in vitro enhance experimental metastasis in vivo.
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PMID:Sublethal oxidative stress inhibits tumor cell adhesion and enhances experimental metastasis of murine mammary carcinoma. 782 Sep 52

There has been considerable interest in identifying specific foods and phytochemicals that may have breast cancer preventive properties. Concord grapes are rich in polyphenolic chemicals and anthocyanin pigments that may have biological properties which could suppress cancer such as having antioxidant, antiproliferative, and proapoptotic actions. To determine the potential breast cancer protective action of purple grape juice, we examined the effect of grape juice consumption on the initiation stage of 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumorigenesis and on the in vivo formation of rat mammary DNA adducts in female Sprague-Dawley rats. Consumption of grape juice significantly inhibited mammary tumor mass at termination and the growth of tumors for the first 5 weeks of detectable tumor development. Consumption of grape juice phenolics by rats also significantly inhibited in vivo mammary DMBA-DNA adduct formation by 34 and 56% for animals fed phenolics at 346 and 692 mg/dL, respectively, compared to controls. Mammary 8-oxo-deoxyguanosine (8-oxo-dG) levels decreased by 25 and 37%, respectively, but the differences were not statistically significant. Liver DMBA-DNA adducts decreased by 10-30%, while 8-oxo-dG adducts remained unchanged, following grape juice intake. Liver glutathione S-transferase activity was significantly increased following grape juice consumption, but only at the highest level of intake. In addition, liver activities of catalase increased and xanthine oxidase decreased significantly, but only at the highest grape juice dose. Thus, these studies indicate that specific constituents or combinations of phytochemicals in purple grape juice can block the initiation stage of DMBA-induced rat mammary tumorigenesis. This tumor inhibitory effect was associated with a suppression of mammary DMBA-DNA adduct formation, which in part may be explained by increased liver activity of the phase II metabolizing enzyme, glutathione S-transferase. Mammary and liver 8-oxo-dG levels were not significantly altered by grape juice consumption. Thus, grape juice constituents appear to have benefit in decreasing susceptibility of the rat mammary gland to the tumor-initiating action of DMBA.
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PMID:Purple grape juice inhibits 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumorigenesis and in vivo DMBA-DNA adduct formation. 1587 97