JBC INTERFERin siRNA transfection reagent

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M201151200 on March 7, 2002

J. Biol. Chem., Vol. 277, Issue 19, 16895-16899, May 10, 2002
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow An addition or correction has been published
Right arrow All Versions of this Article:
277/19/16895    most recent
M201151200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
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 Lutsenko, E. A.
Right arrow Articles by Golde, D. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lutsenko, E. A.
Right arrow Articles by Golde, D. W.

Vitamin C Prevents DNA Mutation Induced by Oxidative Stress*

Eugene A. Lutsenko, Juan M. Cárcamo, and David W. GoldeDagger

From the Memorial Sloan-Kettering Cancer Center, New York, New York 10021

The precise role of vitamin C in the prevention of DNA mutations is controversial. Although ascorbic acid has strong antioxidant properties, it also has pro-oxidant effects in the presence of free transition metals. Vitamin C was recently reported to induce the decomposition of lipid hydroperoxides independent of metal interactions, suggesting that it may cause DNA damage. To directly address the role of vitamin C in maintaining genomic integrity we developed a genetic system for quantifying guanine base mutations induced in human cells under oxidative stress. The assay utilized a plasmid construct encoding the cDNA for chloramphenicol acetyl transferase modified to contain an amber stop codon, which was restored to wild type by G to T transversion induced by oxidative stress. The mutation frequency was determined from the number of plasmids containing the wild type chloramphenicol acetyl transferase gene rescued from oxidatively stressed cells. Cells were loaded with vitamin C by exposing them to dehydroascorbic acid, thereby avoiding transition metal-related pro-oxidant effects of ascorbic acid. We found that vitamin C loading resulted in substantially decreased mutations induced by H2O2. Depletion of glutathione led to cytotoxicity and an increase in H2O2-induced mutation frequency; however, mutation frequency was prominently decreased in depleted cells preloaded with vitamin C. The mutation results correlated with a decrease in total 8-oxo-guanine measured in genomic DNA of cells loaded with vitamin C and oxidatively stressed. These findings directly support the concept that high intracellular concentrations of vitamin C can prevent oxidation-induced mutations in human cells.

* This work was supported by grants from the National Institutes of Health and New York State.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021. Tel.: 212-639-8483; E-mail: d-golde@ski.mskcc.org.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.


This article has been cited by other articles:


Home page
 J. Nutr.Home page
Y. Li and H. E. Schellhorn
New Developments and Novel Therapeutic Perspectives for Vitamin C
J. Nutr., October 1, 2007; 137(10): 2171 - 2184.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
S. T. Durant, K. S. Paffett, M. Shrivastav, G. S. Timmins, W. F. Morgan, and J. A. Nickoloff
UV Radiation Induces Delayed Hyperrecombination Associated with Hypermutation in Human Cells.
Mol. Cell. Biol., August 1, 2006; 26(16): 6047 - 6055.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
Y. Yoshikawa, K. Hizume, Y. Oda, K. Takeyasu, S. Araki, and K. Yoshikawa
Protective Effect of Vitamin C against Double-Strand Breaks in Reconstituted Chromatin Visualized by Single-Molecule Observation
Biophys. J., February 1, 2006; 90(3): 993 - 999.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
S. KC, J. M. Carcamo, and D. W. Golde
Vitamin C enters mitochondria via facilitative glucose transporter 1 (Glut1) and confers mitochondrial protection against oxidative injury
FASEB J, October 1, 2005; 19(12): 1657 - 1667.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
N. Karasavvas, J. M. Carcamo, G. Stratis, and D. W. Golde
Vitamin C protects HL60 and U266 cells from arsenic toxicity
Blood, May 15, 2005; 105(10): 4004 - 4012.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
J. M. Carcamo, A. Pedraza, O. Borquez-Ojeda, B. Zhang, R. Sanchez, and D. W. Golde
Vitamin C Is a Kinase Inhibitor: Dehydroascorbic Acid Inhibits I{kappa}B{alpha} Kinase {beta}
Mol. Cell. Biol., August 1, 2004; 24(15): 6645 - 6652.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
E. A. Lutsenko, J. M. Carcamo, and D. W. Golde
A Human Sodium-Dependent Vitamin C Transporter 2 Isoform Acts as a Dominant-Negative Inhibitor of Ascorbic Acid Transport
Mol. Cell. Biol., April 15, 2004; 24(8): 3150 - 3156.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Clin. Nutr.Home page
K. W. Lee, H. J. Lee, Y.-J. Surh, and C. Y. Lee
Vitamin C and cancer chemoprevention: reappraisal
Am. J. Clinical Nutrition, December 1, 2003; 78(6): 1074 - 1078.
[Abstract] [Full Text] [PDF]

Home page
 Integr Cancer TherHome page
D. W. Golde
Vitamin C in Cancer
Integr Cancer Ther, June 1, 2003; 2(2): 158 - 159.
[PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.