Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Internucleosomal DNA fragmentation and cell death induced by dexamethasone in rat thymocytes were inhibited when cells were cultured in 95% N2/5% CO2 atmosphere, in which oxygen was rapidly reduced to under 0.5%. DNA fragmentation was delayed by a less severe hypoxia in 5% oxygen whilst in cell cultured in high oxygen atmosphere (95% O2) cell death was increased. On the other hand, prolonged oxygen deprivation caused an increase of spontaneous apoptotic cell death. Hypoxia also inhibited DNA fragmentation induced by calcium ionophore A23187, but not by topoisomerase inhibitor camptothecin. These data support the hypothesis of the involvement of oxygen reactive species in calcium-mediated apoptosis and suggest a complex role of oxygen in the modulation of programmed cell death.
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PMID:Oxygen tension influences DNA fragmentation and cell death in glucocorticoid-treated thymocytes. 762 42

Over the past ten years several laboratories have explored the use of perfluorochemical emulsions (PFCE) and carbogen (95% O2/5% CO2; C) or oxygen breathing as an adjuvant to radiation therapy and/or chemotherapy in solid tumor model systems. The rationale for the use of PFCE and C or oxygen breathing in this therapeutic setting is that solid tumor masses contain areas of hypoxia which are therapeutically resistant. Since x-rays and many chemotherapeutic agents require oxygen to be maximally cytotoxic and most normal tissues are well-oxygenated, the additional oxygen put in circulation by the PFCE/C should not increase the normal tissue toxicities produced by the various therapies. Several anticancer agents are dependent on oxygen to be cytotoxic, these drugs such as the iron-chelating peptide bleomycin are enhanced in antitumor activity by the co-administration of a PFCE/C. The antitumor alkylating agents especially cyclophosphamide, BCNU and melphalan show increased tumor cell killing without a concomitant increase in bone marrow toxicity when administered with PFCE/C. Enhanced activity was also observed when topoisomerase II inhibitors such as adriamycin and etoposide were co-administered with PFCE/C. Positive effects, although smaller, were observed when antimetabolites such as 5-fluorouracil and methotrexate were co-administered with PFCE/C.
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PMID:Combination of perfluorochemical emulsions and carbogen breathing with cancer chemotherapy. 784 13

Recently, we reported that alterations in topoisomerase II (topo II) activity appear to contribute to mitomycin C (MMC) resistance in HT-29R13 human colon cancer cells under aerobic conditions. In this study, the expression of topo II alpha and topo II beta in parent HT-29 and MMC resistant variant HT-29R13 cells was investigated under aerobic, acute hypoxic (after 4 hr in 95% N2, 5% CO2 < 0.01% O2), and chronic intermittent hypoxic (after 4 hr hypoxia/day x 7 days) conditions. Acute hypoxia induced topo II alpha mRNA and protein, effects that were more pronounced in HT-29 cells. Chronic intermittent hypoxia caused a decrease in topo alpha mRNA and protein, changes that were again more pronounced in HT-29 cells. The observed changes in topo II alpha protein were associated with parallel changes in topo II activity under all conditions tested. Topo II beta mRNA was expressed at a very low level in both cell lines under aerobic and hypoxic conditions. Compared with cells under aerobic conditions, HT-29 cells were more sensitive to MMC under acute hypoxia but more resistant under chronic intermittent hypoxia. In contrast, the senstivity of HT-29R13 cells was unchanged under acute hypoxia, but the cells were more resistant under chronic intermittent hypoxia. Under all conditions tested, the degree of cytotoxicity corresponded to the frequency of MMC-induced DNA cross-links and topo II alpha protein levels and activity. Our results demonstrated that MMC cytotoxicity in hypoxic cells is highly dependent upon the type of hypoxia and the cell type. Hypoxia has significant effects on topo II alpha expression in HT-29 and HT-29R13 cells which correlate with MMC cytotoxicity.
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PMID:Effect of acute and chronic intermittent hypoxia on DNA topoisomerase II alpha expression and mitomycin C-induced DNA damage and cytotoxicity in human colon cancer cells. 875 40