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ToxSci Advance Access published online on March 14, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm045
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© The Author 2007. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Ku80 Deficiency Does Not Affect Particulate Chromate-Induced Chromosome Damage and Cytotoxicity in Chinese Hamster Ovary Cells

Eric Camrye1, Sandra S. Wise1, Peter Milligan2, Nancy Gordon1, Britton Goodale1, Megan Stackpole1, Natalie Patzlaff1, AbouEl-Makarim Aboueissa3 and John Pierce Wise, Sr1,*

1 Wise Laboratory of Environmental and Genetic Toxicology, Maine Center for Toxicology and Environmental Health, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME. 04104-9300 2 College of Natural and Social Sciences, University of Maine at Augusta, 46 University Drive, Augusta, ME 04330-9410 3 Department of Mathematics & Statistics, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME. 04104-9300

* Corresponding author. Tel.: 207-228-8050; fax: 207-228-8057. E-mail address: John.Wise{at}usm.maine.edu

Received January 18, 2007; revision received February 12, 2007; accepted February 18, 2007


  Abstract

Particulate hexavalent chromium ((Cr(VI)) compounds are human lung carcinogens. These compounds induce DNA damage, chromosome aberrations and concentration-dependent cell death in human and Chinese hamster ovary (CHO) cells. The relationship between Cr(VI) induced DNA damage and chromosome aberrations is poorly understood. Accordingly, this study focused on examining the role of Ku80, a gene involved in non-homologous endjoining (NHEJ) repair, in particulate chromate-induced cytotoxicity and chromosome damage in CHO cells. Three different cell lines were used: CHO-K1 (parental), xrs-6 (Ku80-deficient) and 2E (xrs-6 complemented with Ku80 gene). Levels of cell death were higher in xrs-6 cells when compared to wildtype, suggesting that Ku80 was important for protecting cells from lead chromate. However, Ku80 played no role in protecting cells from particulate Cr(VI)-induced chromosome instability (CIN) as gene complementation with Ku80 (2E cells) studies and uptake experiments showed similar frequency and amounts of chromosome damage between the cell lines and that any observed difference based on administered concentration was actually due to differences in Cr(VI) uptake. The spectrum of chromosome damage was also unaffected by Ku80 deficiency. These data indicate that Ku80 protects cells from cytotoxicity but is not involved in protecting cells from particulate chromate-induced chromosome instability.

Key Words: chromium; chromate; particulate; Ku80; chromosome instability; single strand breaks; nonhomologous endjoining repair.


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