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ToxSci Advance Access originally published online on April 5, 2006
Toxicological Sciences 2006 92(1):96-102; doi:10.1093/toxsci/kfj183
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

XRCC1 Protects against Particulate Chromate–Induced Chromosome Damage and Cytotoxicity in Chinese Hamster Ovary Cells

Eliza Grlickova-Duzevik, Sandra S. Wise, Ray C. Munroe, W. Douglas Thompson and John Pierce Wise, Sr1

Wise Laboratory of Environmental and Genetic Toxicology, Maine Center for Toxicology and Environmental Health, University of Southern Maine, Portland, Maine 04104-9300

Received January 13, 2006; accepted March 29, 2006

Water-insoluble hexavalent chromium compounds are well-established human lung carcinogens. Lead chromate, a model insoluble Cr(VI) compound, induces DNA damage, chromosome aberrations, and dose-dependent cell death in human and Chinese hamster ovary (CHO) cells. The relationship between lead chromate–induced DNA damage and chromosome aberrations is unknown. Our study focus was on examining the role of XRCC1 in lead chromate–induced cytotoxicity and structural chromosomal aberrations in CHO cells. Three different cell lines were used: AA8 (parental), EM9 (XRCC1 mutant), and H9T3 (EM9 complemented with human XRCC1 gene). Cytotoxicity was significantly higher in EM9 cells when compared to AA8 and H9T3 cells, indicating that XRCC1 is important for protecting cells from lead chromate particles–induced cell death. The frequency of damaged metaphase cells was not affected by XRCC1 deficiency. However, the total amount of Cr(VI)-induced chromosome damage was exacerbated by XRCC1 deficiency, and the spectrum of damage changed dramatically. Chromatid and isochromatid lesions were the most prominent aberrations induced in all cell lines. XRCC1 was essential to reduce the formation of chromatid lesions, but not for isochromatid lesions. In addition, XRCC1 deficiency resulted in a dramatic increase in the number of chromatid exchanges, indicating that XRCC1 is involved in protection from lead chromate–induced chromosome instability.

Key Words: chromate; particulate; XRCC1; chromosome instability; single-strand breaks.


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E. Camyre, S. S. Wise, P. Milligan, N. Gordon, B. Goodale, M. Stackpole, N. Patzlaff, A.-M. Aboueissa, and J. P. Wise Sr
Ku80 Deficiency Does Not Affect Particulate Chromate-Induced Chromosome Damage and Cytotoxicity in Chinese Hamster Ovary Cells
Toxicol. Sci., June 1, 2007; 97(2): 348 - 354.
[Abstract] [Full Text] [PDF]


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