Cancer Research Cell Death Mechanisms and Cancer Therapy Telomeres
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gasche, C.
Right arrow Articles by Boland, C. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gasche, C.
Right arrow Articles by Boland, C. R.
[Cancer Research 61, 7444-7448, October 15, 2001]
© 2001 American Association for Cancer Research

Carcinogenesis

Oxidative Stress Increases Frameshift Mutations in Human Colorectal Cancer Cells1

Christoph Gasche2,,3, Christina L. Chang2, Jennifer Rhees, Ajay Goel and C. Richard Boland4

Department of Medicine and Cancer Center, University of California at San Diego, La Jolla, California 92093-0688, and the Research Service of San Diego VA Medical Center, San Diego, California 92161

Chronic inflammation in the gastrointestinal tract increases the risk for development of cancer by an incompletely understood pathway, which may involve microsatellite instability (MSI). Low frequency of MSI referred to as "MSI-L" occurs frequently in chronically inflamed nonneoplastic tissue. In this work, we have tested the hypothesis that oxidative stress may induce the accumulation of frameshift mutations in human microsatellite DNA. Mismatch repair (MMR)-proficient HCT116+chr3 and MMR-deficient HCT116 cells were transfected with pCMV-(CA)13-EGFP, a plasmid that contains a (CA)13 dinucleotide repeat, which disrupts the reading frame of the downstream enhanced green fluorescent protein gene. A dose-dependent increase in frameshift mutations restoring the enhanced green fluorescent protein reading frame was detected in HCT116 by flow cytometry. At 1 mM H2O2, the mutant fraction was 9-fold higher than that in mock-treated control cells. Although demonstrating stability at lower H2O2 concentrations, MMR-proficient HCT116+chr3 cells accumulated mutations at the 1 mM H2O2 level (4.1-fold above mock-treated control). No significant mutations were detected when HCT116 cells were transfected with the pCMV-(N)26-EGFP construct that contains 26 nucleotides in a random sequence. These data indicate that oxidative stress is a potential mutagen leading to accumulation of frameshift mutations and may contribute to MSI in the setting of chronic inflammation.




This article has been cited by other articles:


Home page
 Mol. Cell. Biol.Home page
S. V. Mudrak, C. Welz-Voegele, and S. Jinks-Robertson
The Polymerase {eta} Translesion Synthesis DNA Polymerase Acts Independently of the Mismatch Repair System To Limit Mutagenesis Caused by 7,8-Dihydro-8-Oxoguanine in Yeast
Mol. Cell. Biol., October 1, 2009; 29(19): 5316 - 5326.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
F. Colotta, P. Allavena, A. Sica, C. Garlanda, and A. Mantovani
Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability
Carcinogenesis, July 1, 2009; 30(7): 1073 - 1081.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
C Campregher, M G Luciani, and C Gasche
Activated neutrophils induce an hMSH2-dependent G2/M checkpoint arrest and replication errors at a (CA)13-repeat in colon epithelial cells
Gut, June 1, 2008; 57(6): 780 - 787.
[Abstract] [Full Text] [PDF]

Home page
 MutagenesisHome page
A. M. Skinner, C. Dan, and M. S. Turker
The frequency of CC to TT tandem mutations in mismatch repair-deficient cells is increased in a cytosine run
Mutagenesis, March 1, 2008; 23(2): 87 - 91.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D.-H. Lee, R. S. Esworthy, C. Chu, G. P. Pfeifer, and F.-F. Chu
Mutation accumulation in the intestine and colon of mice deficient in two intracellular glutathione peroxidases.
Cancer Res., October 15, 2006; 66(20): 9845 - 9851.
[Abstract] [Full Text] [PDF]

Home page
 Int J EpidemiolHome page
C.-C. Chen, S.-Y. Yang, C.-J. Liu, C.-L. Lin, Y.-F. Liaw, S.-M. Lin, S.-D. Lee, P.-J. Chen, C.-J. Chen, and M.-W. Yu
Association of cytokine and DNA repair gene polymorphisms with hepatitis B-related hepatocellular carcinoma
Int. J. Epidemiol., December 1, 2005; 34(6): 1310 - 1318.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Shahrzad, L. Quayle, C. Stone, C. Plumb, S. Shirasawa, J. W. Rak, and B. L. Coomber
Ischemia-Induced K-ras Mutations in Human Colorectal Cancer Cells: Role of Microenvironmental Regulation of MSH2 Expression
Cancer Res., September 15, 2005; 65(18): 8134 - 8141.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
C R Boland, M G Luciani, C Gasche, and A Goel
INFECTION, INFLAMMATION, AND GASTROINTESTINAL CANCER
Gut, September 1, 2005; 54(9): 1321 - 1331.
[Full Text] [PDF]

Home page
 Cancer Res.Home page
C. Gasche, A. Goel, L. Natarajan, and C. R. Boland
Mesalazine Improves Replication Fidelity in Cultured Colorectal Cells
Cancer Res., May 15, 2005; 65(10): 3993 - 3997.
[Abstract] [Full Text] [PDF]

Home page
 Sci Aging Knowl EnvironHome page
A. M. Skinner and M. S. Turker
Oxidative Mutagenesis, Mismatch Repair, and Aging
Sci. Aging Knowl. Environ., March 2, 2005; 2005(9): re3 - re3.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
J. A. Satia, T. Keku, J. A. Galanko, C. Martin, R. T. Doctolero, A. Tajima, R. S. Sandler, and J. M. Carethers
Diet, Lifestyle, and Genomic Instability in the North Carolina Colon Cancer Study
Cancer Epidemiol. Biomarkers Prev., February 1, 2005; 14(2): 429 - 436.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
S. H. Itzkowitz and X. Yio
Inflammation and Cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation
Am J Physiol Gastrointest Liver Physiol, July 1, 2004; 287(1): G7 - G17.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
N. L. Komarova and D. Wodarz
The optimal rate of chromosome loss for the inactivation of tumor suppressor genes in cancer
PNAS, May 4, 2004; 101(18): 7017 - 7021.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
L. A. VanderVeen, M. F. Hashim, Y. Shyr, and L. J. Marnett
Induction of frameshift and base pair substitution mutations by the major DNA adduct of the endogenous carcinogen malondialdehyde
PNAS, November 25, 2003; 100(24): 14247 - 14252.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. C. Cabelof, Z. Guo, J. J. Raffoul, R. W. Sobol, S. H. Wilson, A. Richardson, and A. R. Heydari
Base Excision Repair Deficiency Caused by Polymerase {beta} Haploinsufficiency: Accelerated DNA Damage and Increased Mutational Response to Carcinogens
Cancer Res., September 15, 2003; 63(18): 5799 - 5807.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
P. Peltomaki
Role of DNA Mismatch Repair Defects in the Pathogenesis of Human Cancer
J. Clin. Oncol., March 15, 2003; 21(6): 1174 - 1179.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
C. Gasche, C. L. Chang, L. Natarajan, A. Goel, J. Rhees, D. J. Young, C. N. Arnold, and C. R. Boland
Identification of frame-shift intermediate mutant cells
PNAS, February 18, 2003; 100(4): 1914 - 1919.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
C. L. Chang, G. Marra, D. P. Chauhan, H. T. Ha, D. K. Chang, L. Ricciardiello, A. Randolph, J. M. Carethers, and C. R. Boland
Oxidative stress inactivates the human DNA mismatch repair system
Am J Physiol Cell Physiol, July 1, 2002; 283(1): C148 - C154.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2001 by the American Association for Cancer Research.