Human cytochrome P450 reductase can act as a source of endogenous oxidative DNA damage and genetic instability

Free Radical Biology & Medicine
Tina HeineBernd Epe

Abstract

Studies with repair-deficient mice and other experiments suggest that oxidative DNA modifications are generated in all types of cells even under physiological conditions and that this type of endogenous DNA damage contributes to spontaneous cancer incidence. However, the cellular sources of reactive oxygen species that are relevant for nuclear oxidative DNA damage are largely unknown. Here, we report that expression of human NADPH-cytochrome P450 reductase (hOR) in cultured V79 Chinese hamster cells gives rise to elevated basal levels of oxidative purine modifications after depletion of glutathione. Also, the basal levels of micronuclei are increased in the hOR-expressing cells, and again the effect is enhanced when the antioxidant defense system of the cells is diminished by depletion of glutathione. The oxidative DNA damage is increased when duroquinone, a substrate of hOR, is added, both in the presence and absence of glutathione. In contrast, hOR-expressing cells are similarly sensitive as the parental cells when oxidative DNA damage and micronuclei are induced by a mechanism independent of hOR, i.e., exposure to bromate. The results identify hOR as a potential source of endogenous oxidative DNA damage and subsequent geneti...Continue Reading

References

Oct 19, 1976·Biochemistry·K W KohnC A Friedman
Feb 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·N R BachurH Kon
Aug 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·M L MichaelsJ H Miller
Dec 1, 1987·Archives of Biochemistry and Biophysics·G A MooreP J O'Brien
Jan 30, 1981·Biochemical and Biophysical Research Communications·B Bösterling, J R Trudell
Jan 1, 1994·Methods in Enzymology·B Epe, J Hegler
Feb 21, 1998·Proceedings of the National Academy of Sciences of the United States of America·H J HelbockB N Ames
Oct 13, 1999·Mutation Research·A A Morley, D R Turner
Nov 11, 1999·Proceedings of the National Academy of Sciences of the United States of America·A KlunglandD E Barnes
Mar 22, 2000·Proceedings of the National Academy of Sciences of the United States of America·O MinowaT Noda
Jul 11, 2000·Mutagenesis·J L Parsons, J K Chipman
Dec 13, 2000·Mutation Research·M Fenech
Mar 29, 2001·Trends in Genetics : TIG·L J Marnett, J P Plastaras
Jul 2, 2003·Nature Genetics·William G Thilly
Nov 26, 2003·Mutation Research·Svein Bjelland, Erling Seeberg
Mar 3, 2004·Archives of Biochemistry and Biophysics·Andrew R CollinsJose Viña
Mar 6, 2004·Pharmacological Reviews·Martijn RooseboomNico P E Vermeulen
Apr 6, 2004·Biochimica Et Biophysica Acta·Marat B MuratalievF Ann Walker
May 5, 2004·Mutagenesis·Rinne De Bont, Nik van Larebeke
Jan 14, 2005·Molecular and Cellular Biochemistry·Marian ValkoJoshua Telser
Oct 1, 1997·Toxicology in Vitro : an International Journal Published in Association with BIBRA·H HermersdörferH R Glatt

❮ Previous
Next ❯

Citations

May 19, 2009·Free Radical Biology & Medicine·Sandro ArgüellesAntonio Ayala
Feb 21, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Tamara PotikhaDaniel Goldenberg
Feb 27, 2018·Dose-response : a Publication of International Hormesis Society·Carmel MothersillColin Seymour
Jan 13, 2010·Bioconjugate Chemistry·Venkateswaran C PillaiReza Mehvar

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Free Radical Biology & Medicine
Florian L MullerHolly Van Remmen
Free Radical Biology & Medicine
Reshma Shringarpure, Kelvin J A Davies
© 2021 Meta ULC. All rights reserved