dicoumarol/hypoxia

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Cytotoxicity of BMS-181174. Effects of hypoxia, dicoumarol, and repair deficits.

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Ingia / Ingia

The mitomycin C (MC) analog BMS-181174 (previously designated as BMY25067) has been shown to be active against a variety of solid tumors in mice. The activity of this compound against tumor cell lines resistant to MC and the different toxicity profiles of BMS-181174 and MC suggested that there may

Effects of dicoumarol, insulin and anoxia on rat diaphragm. I. Effect on respiration, extra-cellular space and water content.

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Ingia / Ingia

Effects of dicoumarol, insulin and anoxia on rat diaphragm. II. Penetration of sugars.

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Ingia / Ingia

Role of NAD(P)H:(quinone acceptor) oxidoreductase (DT-diaphorase) in activation of mitomycin C under hypoxia.

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Ingia / Ingia

The role of the two-electron reducing enzyme DT-diaphorase in the activation of mitomycin C under hypoxic conditions was investigated. Mitomycin C activity was compared in L5178Y murine lymphoblasts, which have low levels of DT-diaphorase activity, and L5178Y/HBM10 cells, which have elevated levels

Nitroimidazole adducts as markers for tissue hypoxia: mechanistic studies in aerobic normal tissues and tumour cells.

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Ingia / Ingia

Two aspects of the aerobic metabolism of nitroimidazole markers for hypoxia were investigated. Several normal murine tissues which are likely to be well oxygenated bind misonidazole at rates comparable to those of hypoxic regions in tumours. The possibility that this aerobic activation occurs via an

Differential enzymatic reductions governing the differential hypoxia-selective cytotoxicities of phenazine 5,10-dioxides.

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Ingia / Ingia

Some derivatives of phenazine 5,10-dioxide are selectively toxic to hypoxic cells commonly found in solid tumors. Previous studies of the phenazine 5,10-dioxide mechanism of action indicated that a bioreduction process could be involved in its selective toxicities, maybe as result of its potential

Modification of the metabolism and cytotoxicity of bioreductive alkylating agents by dicoumarol in aerobic and hypoxic murine tumor cells.

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Ingia / Ingia

We have demonstrated previously that dicoumarol (DIC) increased the generation of reactive metabolites from mitomycin C (MC) in EMT6 cells under hypoxic conditions in vitro. This increased reaction rate was associated with an increased toxicity of MC to hypoxic EMT6 cells. In contrast, aerobic cells

Factors affecting sensitivity to EO9 in rodent and human tumour cells in vitro: DT-diaphorase activity and hypoxia.

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Ingia / Ingia

Twenty-three human tumour cell lines (lung, breast, and colon) and eight rodent cell lines were evaluated for their sensitivity to the quinone-based anticancer drug EO9 [3-hydroxymethyl-5-aziridinyl-1-methyl-2-(1H indole-4,7-dione)prop-beta-en-alpha-o1]. Sensitivity was compared with the

Baicalein protects rat cardiomyocytes from hypoxia/reoxygenation damage via a prooxidant mechanism.

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Ingia / Ingia

OBJECTIVE Baicalin and its aglycone baicalein are the major flavonoid components of the root of Scutellaria baicalensis. Recent studies have shown that they can attenuate oxidative stress in various in vitro models as they possess potent antioxidant activities. This study investigated alternative

Kinetics of Flavoenzyme-Catalyzed Reduction of Tirapazamine Derivatives: Implications for Their Prooxidant Cytotoxicity.

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Ingia / Ingia

Derivatives of tirapazamine and other heteroaromatic N-oxides (ArN→O) exhibit promising antibacterial, antiprotozoal, and tumoricidal activities. Their action is typically attributed to bioreductive activation and free radical generation. In this work, we aimed to clarify the mechanism(s) of

A unique cytosolic activity related but distinct from NQO1 catalyses metabolic activation of mitomycin C.

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Ingia / Ingia

Mitomycin C (MMC) is a prototype bioreductive drug employed to treat a variety of cancers including head and neck cancer. Among the various enzymes, dicoumarol inhibitable cytosolic NAD(P)H:quinone oxidoreductase1 (NQO1) was shown to catalyse bioreductive activation of MMC leading to cross-linking

Enzymology of mitomycin C metabolic activation in tumour tissue. Characterization of a novel mitochondrial reductase.

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Ingia / Ingia

In this study, the enzymology of mitomycin C (MMC) bioactivation in two murine colon adenocarcinomas, MAC 16 and MAC 26, was examined. Subcellular quinone reductase assessment via cytochrome c reduction confirmed a number of active enzymes. MAC 16 exhibited 22-fold greater levels of cytosolic

Activation of NQO-1 mediates the augmented contractions of isolated arteries due to biased activity of soluble guanylyl cyclase in their smooth muscle.

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Ingia / Ingia

Earlier studies on isolated arteries demonstrated that the para-quinone thymoquinone, like acute hypoxia, induces augmentation of contractions, depending on biased activity of soluble guanylyl cyclase (sGC), generating inosine-3',5'-cyclic monophosphate (cyclic IMP) rather than

Chemotherapeutic attack of hypoxic tumor cells by the bioreductive alkylating agent mitomycin C.

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Ingia / Ingia

Since the cure of solid tumors is limited by the presence of cells with low oxygen contents, we have approached the development of treatment regimens and of new drugs for these tumors by investigating agents which are preferentially bioactivated under hypoxia. Major emphasis has been directed at

Molecular mechanisms of tirapazamine (SR 4233, Win 59075)-induced hepatocyte toxicity under low oxygen concentrations.

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Ingia / Ingia

Previously we showed that tirapazamine (SR 4233, Win 59075) is cytotoxic towards hepatocytes under conditions of hypoxia but not in 10% or 95% oxygen and that bioreduction by DT-diaphorase or cytochrome P450 is not a major pathway. In the present study, we report that tirapazamine is highly

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