Abstract | PURPOSE: EXPERIMENTAL DESIGN: Intraperitoneal ovarian metastases and bladder tumor clinical samples were analyzed for NQO1 and NQO2 activity, mRNA expression by semiquantitative reverse transcription-PCR, and genotype by RFLP analysis. RESULTS: NQO1 activity was higher in the bladder cohort than in the ovarian cohort (0-283 and 0-30 nmol/min/mg, respectively; P < 0.0001). In contrast, NQO2 activity was higher in the ovarian tissue than in the bladder samples (0.15-2.27 and 0-1.14 nmol/min/mg, respectively; P = 0.0004). In both cohorts, the NQO1 C609T single-nucleotide polymorphism (SNP) was associated with approximately 7-fold lower NQO1 activity. The NQO2 exon 3 T14055C SNP was associated with lower NQO2 activity relative to wild-type [median values of 0.18 and 0.37 nmol/min/mg in the bladder samples (P = 0.007) and 0.82 and 1.16 nmol/min/mg in the ovarian cohort (P = 0.034)]. CONCLUSION: This is the first observation reporting an apparent association between an NQO2 exon 3 SNP and lower enzymatic activity. The high NQO2 activity of intraperitoneal ovarian metastases relative to other tissues indicates a potential for tretazicar therapy in the treatment of this disease. In contrast, the low level of NQO1 activity and expression relative to other tissues suggests that NQO1-directed therapies would not be appropriate.
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Authors | David Jamieson, Kerrie Wilson, Simon Pridgeon, Jane P Margetts, Richard J Edmondson, Hing Y Leung, Richard Knox, Alan V Boddy |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 13
Issue 5
Pg. 1584-90
(Mar 01 2007)
ISSN: 1078-0432 [Print] United States |
PMID | 17332305
(Publication Type: Journal Article)
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Chemical References |
- Pyridinium Compounds
- nicotinamide-beta-riboside
- Niacinamide
- NAD(P)H Dehydrogenase (Quinone)
- NQO1 protein, human
- NRH - quinone oxidoreductase2
- Quinone Reductases
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Topics |
- Female
- Humans
- NAD(P)H Dehydrogenase (Quinone)
(genetics, metabolism)
- Niacinamide
(analogs & derivatives, metabolism)
- Ovarian Neoplasms
(enzymology, genetics)
- Polymorphism, Restriction Fragment Length
- Polymorphism, Single Nucleotide
- Pyridinium Compounds
- Quinone Reductases
(genetics, metabolism)
- Reverse Transcriptase Polymerase Chain Reaction
- Urinary Bladder Neoplasms
(enzymology, genetics)
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