Abstract
A point mutation in the mRNA of NADP(H): quinone oxidoreductase 1 (NQO1, DT-diaphorase) is believed to be responsible for reduced enzyme activity in the adenocarcinoma BE cell line. The present study examined nine cultured human non-cancerous fibroblast cell strains, five of which were from members of a single cancer-prone family, which demonstrated widely varying activity levels of DT-diaphorase (41 - 3462 nmol min-1 mg-1 protein), to determine if genetic alteration of the NQO1 or NOQ2 gene was involved in determining enzyme activity. All cell strains expressed NQO1 and NQO2 mRNA as measured by a quantitative polymerase chain reaction amplification technique. No relationship was found between the level of mRNA expressed and the enzyme activity in the cells. Sequencing of the entire complementary DNA from the cell strains revealed only a single base substitution at nucleotide 609 in one allele encoding NQO1 in every cell strain from members of the cancer-prone family, except for one cell strain which expressed only the T at nucleotide 609 in both alleles. Subsequent examination of genomic DNA from 44 individuals revealed that this base substitution is present in approximately 50% of the population. The presence of the T at nucleotide 609 in the NQO1 locus does not appear to be directly causal for altered DT-diaphorase activity.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 24 print issues and online access
$259.00 per year
only $10.79 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kuehl, B., Paterson, J., Peacock, J. et al. Presence of a heterozygous substitution and its relationship to DT-diaphorase activity. Br J Cancer 72, 555–561 (1995). https://doi.org/10.1038/bjc.1995.373
Issue Date:
DOI: https://doi.org/10.1038/bjc.1995.373
This article is cited by
-
Associations between nine candidate genetic polymorphisms with coronary heart disease
Herz (2020)
-
Integrated multiomics analysis of hepatoblastoma unravels its heterogeneity and provides novel druggable targets
npj Precision Oncology (2020)
-
Association of cytochrome P4502E1 and NAD(P)H:quinone oxidoreductase 1 genetic polymorphisms with susceptibility to large artery atherosclerotic ischemic stroke: a case–control study in the Turkish population
Neurological Sciences (2017)
-
Gene polymorphisms in the ornithine decarboxylase–polyamine pathway modify gastric cancer risk by interaction with isoflavone concentrations
Gastric Cancer (2015)
-
The NQO1 Pro187Ser polymorphism and breast cancer susceptibility: evidence from an updated meta-analysis
Diagnostic Pathology (2014)