Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.7 (adenine phosphoribosyltransferase)
 692 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To examine the effect of 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylic acid (TEI-6720), an inhibitor of xanthine oxidase, on purine metabolism in the lung cancer cell line A549, the activities of adenosine deaminase, purine nucleoside phosphorylase, adenine phosphoribosyltransferase, hypoxanthine guanine phosphoribosyltransferase, xanthine oxidase, and guanase together with pyrimidine nucleoside phosphorylase were measured with or without the addition of TEI-6720, and the extracellular concentrations of hypoxanthine, xanthine, inosine, uracil, and uridine were measured after the addition of inosine or uridine to the incubation medium with or without TEI-6720. Moreover, the Na-independent nucleoside transport was determined in A549 cells with or without TEI-6720. TEI-6720 inhibited the activity of xanthine oxidase in A549 cells, but did not affect other enzymes. During incubation, TEI-6720 not only prevented a decrease in the inosine concentration in inosine-containing medium, but also a decrease in the uridine concentration in uridine-containing medium. Furthermore, the Na-independent transport of uridine was inhibited by TEI-6720 with a K(i) value of 4.1 micromol/l. These results indicate that TEI-6720 is an inhibitor of the Na-independent nucleoside transport of uridine and inosine, as well as xanthine oxidase.
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PMID:Effect of TEI-6720, a xanthine oxidase inhibitor, on the nucleoside transport in the lung cancer cell line A549. 1062 41

Chromium(VI) [Cr(VI)], a ubiquitous environmental contaminant, is a well-known carcinogen to both humans and experimental animals, although it is a weak mutagen by itself. Occupational exposure to Cr(VI) is strongly associated with a high incidence of lung cancer, but the underlying mechanisms remain unclear. Tobacco smoking is the major cause of lung cancer, and polycyclic aromatic hydrocarbons (PAHs) in tobacco smoke are the major etiological agents. Since humans are frequently exposed to both Cr(VI) and PAHs, it is possible that Cr(VI) and PAHs have a synergistic effect on mutagenecity and cytotoxicity that contributes to the high incidence of lung cancer associated with exposure to both agents. In this study, we tested this possibility by determining the effect of Cr(VI) exposure on (+/-)-anti-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE, an active metabolite of PAHs) induced cytotoxicity, mutagenicity, and DNA adduct formation in Chinese hamster ovary (CHO) cells. Using the adenine phosphoribosyltransferase (APRT(+)) --> APRT(-) forward mutation assay, we found that while Cr(VI) alone induced low mutation frequency, it greatly enhanced BPDE-induced mutations in nucleotide excision repair (NER)-proficient CHO cells. Cr(VI) exposure also greatly enhanced BPDE-induced killing in NER-proficient cells. It is known that the cytotoxicity and mutagenicity of BPDE are mainly caused by the formation of DNA adduct, which are removed by NER. To test the possibility that the enhancement of cytotoxicity and mutagenicity by Cr(VI) is caused by the inhibition of NER, NER-deficient cells were used, and the enhancement effects of Cr(VI) were not observed in those cells. We further found that while Cr(VI) exposure does not change the total BPDE-DNA adduct formation, it significantly inhibited the repair of BPDE-DNA adducts from genomic DNA in NER-proficient cells. Using a host cell reactivation assay, we found that the repair of BPDE-DNA adduct in a luciferase reporter gene is greatly inhibited after Cr(VI) exposure in NER-proficient cells while not in NER-deficient cells. Together these results clearly demonstrate that Cr(VI) exposure can greatly enhance the mutagenicity and cytotoxicity of PAHs by inhibiting the cellular NER pathway, and this may constitute an important mechanism for Cr(VI)-induced human carcinogenesis.
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PMID:Chromium(VI) enhances (+/-)-anti-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene-induced cytotoxicity and mutagenicity in mammalian cells through its inhibitory effect on nucleotide excision repair. 1551 79

In both males and females, lung cancer is one of the most lethal cancers worldwide and accounts for >30% of cancer-related deaths. Despite advances in biomarker analysis and tumor characterization, there remains a need to find suitable biomarker antigen targets for treatment in late-stage lung cancer. Previous research on the salvage pathway enzyme TK1 shows a unique relationship with cancer patients as serum levels are raised according to cancer grade. To expand this analysis, the other salvage pathway enzymes were evaluated for possible upregulation within lung cancer. Adenine phosphoribosyltransferase, deoxycytidine kinase, and hypoxanthine guanine phosphoribosyltransferase (HPRT) were assessed for their presentation on two non-small-cell lung cancer cell lines NCI-H460 and A549. In the present study, we show that deoxycytidine kinase and adenine phosphoribosyltransferase have no significant relationship with the membrane of NCI-H460 cells. However, we found significant localization of HPRT to the membrane of NCI-H460 and A549 cells. When treated with anti-HPRT antibodies, the average fluorescence of the cell population increased by 24.3% and 12.9% in NCI-H460 and A549 cells, respectively, in comparison with controls. To ensure that expression was not attributed to cytoplasmic HPRT, confocal microscopy was performed to visualize HPRT binding on the plasma membrane. After staining NCI-H460 cells treated with both fluorescent antibodies and a membrane-specific dye, we observed direct overlap between HPRT and the membrane of the cancer cells. Additionally, gold-conjugated antibodies were used to label and quantify the amount of HPRT on the cell surface using scanning electron microscopy and energy-dispersive analysis X-ray. Further confirming HPRT presence, the gold weight percentage of the sample increased significantly when NCI-H460 cells were exposed to HPRT antibody (P=0.012) in comparison with isotype controls. Our results show that HPRT is localized on the surface of these non-small-cell lung cancer cell lines.
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PMID:Non-small-cell lung cancer cell lines A549 and NCI-H460 express hypoxanthine guanine phosphoribosyltransferase on the plasma membrane. 2840 44