Reduction of Mitomycin C is Catalysed by Human Recombinant NRH:quinone Oxidoreductase 2 Using Reduced Nicotinamide Adenine Dinucleotide As an Electron Donating Co-factor

Overview

Journal Br J Cancer

Specialty Oncology

Date 2006 Oct 13

PMID 17031400

Citations 10

Authors

D Jamieson

A T Y Tung

R J Knox

A V Boddy

Affiliations

Soon will be listed here.

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.

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