Skip Navigation



Mutagenesis Advance Access published online on September 29, 2005
Mutagenesis, doi:10.1093/mutage/gei056
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
20/6/417    most recent
gei056v1
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 Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Stearns, D. M.
Right arrow Articles by Lantz, R. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Stearns, D. M.
Right arrow Articles by Lantz, R. C.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
Received January 27, 2005
Revised August 11, 2005
Accepted August 14, 2005

Original article

Uranyl acetate induces hprt mutations and uranium-DNA adducts in Chinese hamster ovary EM9 cells

Diane M. Stearns 1*, Monica Yazzie 1, Andrew S. Bradley 1, Virginia H. Coryell 1, Jake T. Shelley 1, Adam Ashby 1, Craig S. Asplund 1, and R. Clark Lantz 2

1 Department of Chemistry and Biochemistry, Northern Arizona University, PO Box 5698, Flagstaff, AZ 86011-5698, USA
2 Department of Cell Biology and Anatomy, University of Arizona, Tucson, AZ, USA

* To whom correspondence should be addressed.
Diane M. Stearns, E-mail: Diane.Stearns{at}nau.edu


  Abstract

Questions about possible adverse health effects from exposures to uranium have arisen as a result of uranium mining, residual mine tailings and use of depleted uranium in the military. The purpose of the current study was to measure the toxicity of depleted uranium as uranyl acetate (UA) in mammalian cells. The activity of UA in the parental CHO AA8 line was compared with that in the XRCC1-deficient CHO EM9 line. Cytotoxicity was measured by clonogenic survival. A dose of 200 µM UA over 24 h produced 3.1-fold greater cell death in the CHO EM9 than the CHO AA8 line, and a dose of 300 µM was 1.7-fold more cytotoxic. Mutagenicity at the hypoxanthine (guanine) phosphoribosyltransferase (hprt) locus was measured by selection with 6-thioguanine. A dose of 200 µM UA produced ~5-fold higher averaged induced mutant frequency in the CHO EM9 line relative to the CHO AA8 line. The generation of DNA strand breaks was measured by the alkaline comet assay at 40 min and 24 h exposures. DNA strand breaks were detected in both lines; however a dose response may have been masked by U-DNA adducts or crosslinks. Uranium-DNA adducts were measured by inductively coupled plasma optical emission spectroscopy (ICP-OES) at 24 and 48 h exposures. A maximum adduct level of 8 U atoms/103 DNA-P for the 300 µM dose was found in the EM9 line after 48 h. This is the first report of the formation of uranium-DNA adducts and mutations in mammalian cells after direct exposure to a depleted uranium compound. Data suggest that uranium could be chemically genotoxic and mutagenic through the formation of strand breaks and covalent U-DNA adducts. Thus the health risks for uranium exposure could go beyond those for radiation exposure.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Toxicol SciHome page
G. C.-T. Jiang, K. Tidwell, B. A. McLaughlin, J. Cai, R. C. Gupta, D. Milatovic, R. Nass, and M. Aschner
Neurotoxic Potential of Depleted Uranium Effects in Primary Cortical Neuron Cultures and in Caenorhabditis elegans
Toxicol. Sci., October 1, 2007; 99(2): 553 - 565.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
C. Thiebault, M. Carriere, S. Milgram, A. Simon, L. Avoscan, and B. Gouget
Uranium Induces Apoptosis and Is Genotoxic to Normal Rat Kidney (NRK-52E) Proximal Cells
Toxicol. Sci., August 1, 2007; 98(2): 479 - 487.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.