XRCC1 protects against particulate chromate-induced chromosome damage and cytotoxicity in Chinese hamster ovary cells.
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.
Grlickova-Duzevik
Eliza
E
Wise Laboratory of Environmental and Genetic Toxicology, Maine Center for Toxicology and Environmental Health, University of Southern Maine, 96 Falmouth Street, Portland, ME 04104-9300, USA.
Wise
Sandra S
SS
Munroe
Ray C
RC
Thompson
W Douglas
WD
Wise
John Pierce
JP
D000818:Animals; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects*; D002840:Chromates / Q000633:toxicity*; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D004268:DNA-Binding Proteins / Q000502:physiology*; D000076105:X-ray Repair Cross Complementing Protein 1
D002840:Chromates; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human