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

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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

Nitric oxide synthase and NADPH-diaphorase after acute hypobaric hypoxia in the rat caudate putamen.

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Changes in the production system of nitric oxide (NO), a multifunctional biological messenger known to participate in blood-flow regulation, neuromodulation, and neuroprotection or neurotoxicity, were investigated in the caudate putamen of adult rats submitted to hypobaric hypoxia. Employing

Interaction of heat and hypoxia in modulating transcription of DT diaphorase in human colon adenocarcinoma cells.

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To study the regulation of the human detoxicating enzyme DT diaphorase (DTD) under hypoxic conditions, we examined the effects of heat and hypoxia, and their interaction, on the steady-state levels of mRNA and DTD enzyme activity in human colon adenocarcinoma HT29 cells. We found that a 1-h heat

Selective sparing of NADPH-diaphorase neurons in neonatal hypoxia-ischemia.

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Excitatory amino acids have been implicated in ischemic neuronal injury. To test this hypothesis in neonatal hypoxia-ischemia, lesions of the cortex and striatum were induced in 7-day-old rats by unilaterally ligating their carotid arteries and subjecting them to hypoxic conditions for 2 hours.

[Localization of NADPH diaphorase in central nervous system of the chiton Leptochiton assimilis in normal conditions and during hypoxia].

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By light and electron microscope histochemical and cytochemical methods, the localization and activity of NADPH-diaphorase (NADPH-d) were studied in the central nervous system (CNS) of the chiton in control and after hypoxia. After acute hypoxia, the enzymatic activity increased in all regions of

Involvement of NF-kappa B in the induction of NAD(P)H:quinone oxidoreductase (DT-diaphorase) by hypoxia, oltipraz and mitomycin C.

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The activity of the two-electron bioreductive enzyme DT-diaphorase (DTD) is induced by heat shock, hypoxic stress, oltipraz, and mitomycin C (MMC). Transcriptional induction is associated with nuclear factor binding to elements mediating immediate early response including AP-1, though the DTD mRNA

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

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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

The importance of DT-diaphorase and hypoxia in the cytotoxicity of RH1 in human breast and non-small cell lung cancer cell lines.

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The diaziridiny/benzoquinone RH1 is shortly to enter a phase I clinical trial. The drug was originally designed as a substrate for the enzyme DT-diaphorase (DTD) such that metabolic activation of the drug would lead to toxicity. To evaluate this, we have measured the toxicity of RH1 in a pair of

Relative importance of DT-diaphorase and hypoxia in the bioactivation of EO9 by human lung tumor cell lines.

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OBJECTIVE Although a number of bioreductive agents are substrates for purified DT-diaphorase the role of this enzyme in either activation or detoxification of these agents in the whole cell is unclear. The aim of this study was to determine the role of DT-diaphorase in the metabolic activation of

[Effect of kainate on the number of NADPH-diaphorase positive neurons in the hippocampus in rats exposed to chronic hypoxia during early ontogenesis].

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Bioreduction activated prodrugs of camptothecin: molecular design, synthesis, activation mechanism and hypoxia selective cytotoxicity.

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Several water-soluble derivatives (CPT3, CPT3a-d) of camptothecin (CPT) were synthesized, among which CPT3 bearing an N,N'-dimethyl-1-aminoethylcarbamate side-chain was further conjugated with reductively eliminating structural units of indolequinone, 4-nitrobenzyl alcohol and 4-nitrofuryl alcohol

Transient block of respiratory chain by cyanide triggers NADPH-diaphorase activity (a marker for nitric oxide synthase) in Dunning rat prostatic epithelium.

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Synthesis of nitric oxide (NO) has been shown in the glandular epithelium of human prostate, with highest levels in the peripheral zone. This location is believed to be the main source of prostatic cancer. The ability of stromal cells to produce NO may contribute to the malignant process. Since

Selective destruction of nitric oxide synthase neurons with quisqualate reduces damage after hypoxia-ischemia in the neonatal rat.

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The vulnerability of the developing CNS to hypoxia-ischemia (H-I) differs from that of the mature brain and is due in part to release of nitric oxide (NO) from parenchymal neurons. If NO is important in the generation of excitotoxic injury after H-I in the developing CNS, then selective destruction

Altered production of nitric oxide and reactive oxygen species in rat nodose ganglion neurons during acute hypoxia.

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Nitric oxide (NO) production in the sensory neurons of the rad nodose ganglion was studied by examining the distribuiotn of NO synthase (NOS) by use of NADPH diaphorase (NADPHD) histochemistry and immunohistochemistry ofr the presence of isoformes of NOS: neuronal (nNOS), endothelial (eNOS) and the

The role of DT-diaphorase in determining the sensitivity of human tumor cells to tirapazamine (SR 4233).

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OBJECTIVE To determine the dependency of the aerobic and hypoxic toxicity of tirapazamine on the intracellular activity of DT-diaphorase. METHODS A panel of 18 human cell lines comprising predominantly small cell and nonsmall cell lung cancer and breast cancer lines were used. The activity of

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