Role of the Fancg gene in protecting cells from particulate chromate-induced chromosome instability

Savery, Laura C.; Grlickova-Duzevik, Eliza; Wise, Sandra S.; Thompson, W. Douglas; Hinz, John M.; Thompson, Larry H.; Wise, John Pierce

doi:10.1016/j.mrgentox.2006.09.005

Cited by 5 publications

(6 citation statements)

References 36 publications

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“…These data are consistent with our previous reports showing that cells deficient in Ku80, FANCG and XRCC1 are also sensitive to the cytotoxic effects of particulate Cr(VI) [33,28,20]. They are also consistent with a previous study of soluble chromate showing that XRCC3-and BRCA2-deficient cells were more sensitive to its cytotoxicity [23].…”

Section: Discussionsupporting

confidence: 93%

“…In this study, and in previous reports using DNA-repair defective cells, we find that DNA repair-deficient cells, including those deficient in Ku80, XRCC1, and FANCG, exhibited large differences in the levels of intracellular genotoxic chemicals compared to their parental and gene complemented control cells [33,20,28]. Such differences in uptake can potentially reverse the conclusions of the relative sensitivities of a cell strain to an agent based only on administered dose.…”

Section: Discussionsupporting

confidence: 62%

“…We used the well-characterized XRCC3-deficient Chinese hamster ovary (CHO) cell line model system of irs1SF [26], and the XRCC3 cDNA complimented 1SFwt8 [27] cell lines to examine the role of XRCC3. The effect of Cr (VI) on the CIN of the wildtype parental AA8 CHO cells, from which the irs1SF cells were derived, has been characterized previously [28].…”

Section: Cells and Cell Culturementioning

confidence: 99%

“…The irs3 cell line, derived from the parental V79 cells, is deficient in RAD51C gene, and are used with their cDNA-complimented cell line irs3#6 [29][30].For further information, we have previously published the details and validation of these cells elsewhere [27][28][29][30].…”

Section: Cells and Cell Culturementioning

confidence: 99%

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Homologous recombination repair protects against particulate chromate-induced chromosome instability in Chinese hamster cells

Stackpole

Wise

Goodale

et al. 2007

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

Self Cite

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Particulate hexavalent chromium [Cr(VI)] compounds are well-established human carcinogens. Cr (VI)-induced tumors are characterized by chromosomal instability (CIN); however, the mechanisms of this effect are unknown. We investigated the hypothesis that homologous recombination (HR) repair of DNA double strand breaks protect cells from Cr(VI)-induced CIN by focusing on the XRCC3 and RAD51C genes, which play an important role in cellular resistance to DNA double strand breaks. We used Chinese hamster cells defective in each HR gene (irs3 for RAD51C and irs1SF for XRCC3) and compared with their wildtype parental and cDNA-complemented controls. We found that the intracellular Cr ion levels varied among the cell lines after particulate chromate treatment. Importantly, accounting for differences in Cr ion levels, we discovered that XRCC3 and RAD51C cells treated with lead chromate had increased cytotoxicity and chromosomal aberrations, relative to wild-type and cDNA-complimented cells. We also observed the emergence of high levels of chromatid exchanges in the two mutant cell lines. For example, 1 ug/cm 2 lead chromate induced 20 and 32 exchanges in XRCC3-and RAD51C-deficient cells, respectively, whereas no exchanges were detected in the wildtype and cDNA-complemented cells. These observations suggest that HR protects cells from Cr(VI)-induced CIN, consistent with the ability of particulate Cr(VI) to induce double strand breaks.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 62%

Section: Cells and Cell Culturementioning

confidence: 99%

Section: Cells and Cell Culturementioning

confidence: 99%

See 2 more Smart Citations

Homologous recombination repair protects against particulate chromate-induced chromosome instability in Chinese hamster cells

Stackpole

Wise

Goodale

et al. 2007

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

Self Cite

View full text Add to dashboard Cite

show abstract

“…We found that Ku80-deficient cells are more sensitive to the cytotoxic effects of particulate Cr(VI). These data are consistent with reports that show that cells deficient in XRCC1 and FANCG are also sensitive to the cytotoxic effects of particulate Cr(VI) (Grlickova-Duzevick et al, 2006a;Savery et al, 2007). However, unlike in those reports, here there was no effect on CIN.…”

Section: Ku80 Deficiency and Cr(vi)-induced Chromosome Damage And Cytsupporting

confidence: 93%

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

Camyre

Wise

Milligan

et al. 2007

Toxicological Sciences

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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 nonhomologous end-joining 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 wild type, 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 CIN.

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A role for Mus81 in the repair of chromium-induced DNA damage

Tamblyn

Sarras

et al. 2009

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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Role of the Fancg gene in protecting cells from particulate chromate-induced chromosome instability

Cited by 5 publications

References 36 publications

Homologous recombination repair protects against particulate chromate-induced chromosome instability in Chinese hamster cells

Homologous recombination repair protects against particulate chromate-induced chromosome instability in Chinese hamster cells

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

A role for Mus81 in the repair of chromium-induced DNA damage

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