Abstract
NRH:Quinone Oxidoreductase 2 (NQO2) has been described as having no enzymatic activity with nicotinamide adenine dinucleotide (NADH) or NADPH as electron donating cosubstrates. Mitomycin C (MMC) is both a substrate for and a mechanistic inhibitor of the NQO2 homologue NQO1. NRH:quinone oxidoreductase 2 catalysed the reduction of MMC at pH 5.8 with NADH as a co-factor. This reaction results in species that inhibit the NQO2-mediated metabolism of CB1954. In addition, MMC caused an increase in DNA cross-links in a cell line transfected to overexpress NQO2 to an extent comparable to that observed with an isogenic NQO1-expressing cell line. These data indicate that NQO2 may contribute to the metabolism of MMC to cytotoxic species.
MeSH terms
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Alkylating Agents / chemistry
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Alkylating Agents / metabolism
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Alkylating Agents / pharmacology
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Animals
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Aziridines / chemistry
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Aziridines / metabolism
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Catalysis / drug effects
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Cell Line
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Comet Assay
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Electron Transport / drug effects
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Humans
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Mitomycin / chemistry
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Mitomycin / metabolism*
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Mitomycin / pharmacology
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NAD / chemistry
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NAD / metabolism*
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NAD(P)H Dehydrogenase (Quinone) / antagonists & inhibitors
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NAD(P)H Dehydrogenase (Quinone) / genetics
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NAD(P)H Dehydrogenase (Quinone) / metabolism
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Oxidation-Reduction
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Quercetin / pharmacology
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Quinone Reductases / antagonists & inhibitors
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Quinone Reductases / genetics
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Quinone Reductases / metabolism*
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Recombinant Proteins / metabolism
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Transfection
Substances
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Alkylating Agents
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Aziridines
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Recombinant Proteins
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NAD
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Mitomycin
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tretazicar
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Quercetin
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NAD(P)H Dehydrogenase (Quinone)
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NQO1 protein, human
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NRH - quinone oxidoreductase2
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Quinone Reductases