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Carcinogenesis Advance Access first published online on April 13, 2007
This version published online on April 17, 2007
Carcinogenesis, doi:10.1093/carcin/bgm093
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Bcl-2 overexpression promotes genomic instability by inhibiting apoptosis of cells exposed to hydrogen peroxide

Andrew G. Cox1,2 and Mark B. Hampton1

1 Free Radical Research Group, Department of Pathology, Christchurch School of Medicine & Health Sciences, University of Otago, Christchurch, New Zealand
2 School of Biological Sciences, University of Canterbury, Christchurch, New Zealand

Corresponding author: Dr Mark Hampton, Department of Pathology, Christchurch School of Medicine & Health Sciences, PO Box 4345, Christchurch, New Zealand, Tel: + 64 3 364 1524, Fax: + 64 3 364 1083, E-mail: mark.hampton{at}chmeds.ac.nz

The anti-apoptotic oncogene bcl-2 is hypothesised to increase the antioxidant status of cells, thereby protecting them from oxidative stress. In this study we examined H2O2-mediated oxidative stress in Jurkat T lymphoma cells. Overexpression of Bcl-2 did not inhibit cytotoxicity at doses of H2O2 that caused necrosis (> 200 µM), but it did block cell death at apoptotic doses (< 200 µM). However, these cells exhibited the same initial level of protein and lipid oxidation following exposure to H2O2 as the parental cells, indicating that the anti-apoptotic activity is not associated with general antioxidant properties. Bcl-2 expression was able to protect against secondary protein carbonyl formation, which was linked to lysosome stabilization. Assessment of micronuclei formation in cells overexpressing Bcl-2 showed evidence of increased genomic instability, consistent with the impairment of apoptosis in damaged cells. We conclude that while Bcl-2 can block cytotoxicity associated with apoptosis-inducing levels of oxidative stress, it does not protect the cells from the stress itself. Bcl-2 may promote tumourigenesis by preventing the removal of oxidatively damaged cells.

Key Words: oxidative stress • apoptosis • micronuclei

The figures have been added in this version.

Received December 21, 2006; revised April 3, 2007; accepted April 4, 2007.


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