Oxidative Stress Induces Mitochondrial DNA Damage and Cytotoxicity through Independent Mechanisms in Human Cancer CellsReport as inadecuate




Oxidative Stress Induces Mitochondrial DNA Damage and Cytotoxicity through Independent Mechanisms in Human Cancer Cells - Download this document for free, or read online. Document in PDF available to download.

BioMed Research InternationalVolume 2013 2013, Article ID 825065, 8 pages

Review ArticleDivision of Urology, Department of Surgery, Research Institute of McGill University Health Center, Room R1-107, 1650 Cedar Avenue, Montreal, QC, Canada H3G 1A4

Received 9 June 2012; Revised 22 August 2012; Accepted 23 August 2012

Academic Editor: Ryan Parr

Copyright © 2013 Yue Han and Junjian Z. Chen. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Intrinsic oxidative stress through increased production of reactive oxygen species ROS is associated with carcinogenic transformation, cell toxicity, and DNA damage. Mitochondrial DNA mtDNA is a natural surrogate to oxidative DNA damage. MtDNA damage results in the loss of its supercoiled structure and is readily detectable using a novel, supercoiling-sensitive real-time PCR method. Our studies have demonstrated that mtDNA damage, as measured by DNA strand breaks and copy number depletion, is very sensitive to exogenous H2O2 but independent of endogenous ROS production in both prostate cancer and normal cells. In contrast, aggressive prostate cancer cells exhibit a more than 10-fold sensitivity to H2O2-induced cell toxicity than normal cells, and a cascade of secondary ROS production is a critical determinant to the differential response. We propose a new paradigm to account for different mechanisms governing cellular oxidative stress, cell toxicity, and DNA damage with important ramifications in devising new techniques and strategies in prostate cancer prevention and treatment.





Author: Yue Han and Junjian Z. Chen

Source: https://www.hindawi.com/



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