Deficient repair of particulate hexavalent chromium-induced DNA double strand breaks leads to neoplastic transformation

Xie, Hong; Wise, Sandra S.; Wise, John Pierce

doi:10.1016/j.mrgentox.2007.09.008

Cited by 29 publications

(18 citation statements)

References 28 publications

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“…It is able to form DNA adduct-based lesions, which lead to stalled replication forks and ultimately double strand breaks [39–42,44,45]. These DSBs overwhelm the repair systems of the cells which then go unrepaired or are mis-repaired leading to translocations and other structural aberrations [56,57]. The accumulation of DSBs also causes a G2 arrest leading to centrosome amplification and spindle assembly checkpoint bypass which lead to aneuploidy [58,59].…”

Section: Chromium (Vi)mentioning

confidence: 99%

Chromium and genomic stability

Wise

2012

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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Many metals serve as micronutrients which protect against genomic instability. Chromium is most abundant in its trivalent and hexavalent forms. Trivalent chromium has historically been considered an essential element, though recent data indicate that while it can have pharmacological effects and value, it is not essential. There are no data indicating that trivalent chromium promotes genomic stability and, instead may promote genomic instability. Hexavalent chromium is widely accepted as highly toxic and carcinogenic with no nutritional value. Recent data indicate that it causes genomic instability and also has no role in promoting genomic stability.

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Section: Chromium (Vi)mentioning

confidence: 99%

Chromium and genomic stability

Wise

2012

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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“…DNA double-strand break (DSB) is the most serious type of damage, and the unpaired or incorrectly repaired DSB could lead to genomic instability. 2 , 3 In mammalian cells, DSB can be repaired mainly by non-homologous end joining (NHEJ) pathway, involving several DSB repair genes, such as X-ray repair complementing defective repair in Chinese hamster cells 6 ( XRCC6 ). 4 Genetic variations in NHEJ genes, such as single nucleotide polymorphism (SNP) might escape cell checkpoint surveillance, and can lead to suboptimal DNA repair, allowing DNA damage to accumulate, and finally trigger tumor initiation.…”

Section: Introductionmentioning

confidence: 99%

Association Between the XRCC6 Polymorphisms and Cancer Risks

et al. 2015

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A number of studies have been carried out to investigate the association of X-ray repair complementing defective repair in Chinese hamster cells 6 (XRCC6) polymorphisms and cancer risks, and the results remained inconsistent and inconclusive.To assess the effect of XRCC6 polymorphisms on cancer susceptibility, we conducted a meta-analysis, up to May 23rd 2014, 6267 cases with different types of tumor and 7536 controls from 20 published case–control studies. Summary odds ratios and corresponding 95% confidence intervals for XRCC6 polymorphism and cancer risk were estimated using fixed- or random-effects models when appropriate. Heterogeneity was assessed by chi-squared-based Q-statistic test, and the sources of heterogeneity were explored by subgroup analyses, logistic meta-regression analyses and Galbraith plot. Publication bias was evaluated by Begg funnel plot and Egger test. Sensitivity analyses were also performed.The rs2267437 polymorphism was associated with a significant increase in risks of overall cancers, breast cancer, renal cell carcinoma and hepatocellular carcinoma, and it could increase the cancer risk in Asian population; the rs5751129 polymorphism could increase the cancer risk in overall cancers; the rs132770 polymorphism was associated with the increased renal cell carcinoma risk; furthermore, the rs132793 polymorphism could decrease breast cancer risk and increase risks in “other cancers”.Overall, the results provided evidences that the single nucleotide polymorphisms in XRCC6 promoter region might play different roles in various cancers, indicating different cancers have different tumorigenesis mechanisms. Our studies may perhaps supplement for the disease monitoring of cancers in the future, and additional studies to determine the exact molecular mechanism might provide us with interventions to protect the susceptible subgroups.

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“…Some in vitro studies have used the sensitive comet assay to investigate genotoxic eff ects of chromate (Hodges et al, 2001;Blasiak and Kowalik, 2000;Lee et al, 2004Lee et al, , 2005Xie et al, 2005Xie et al, , 2008Smart et al, 2006;Liu et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Direct‐oxidative DNA damage and apoptosis induction in different human respiratory cells exposed to low concentrations of sodium chromate

Cavallo

Ursini

Fresegna

et al. 2009

J of Applied Toxicology

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The mechanism of Cr(VI) genotoxicity has still not been elucidated. We used Fpg-modified comet assay to assess direct-oxidative DNA damage on human lung (A549) and bronchial (BEAS-2B) cells exposed to 0.1, 0.5, 1.0 and 10 microm sodium chromate for 0.5, 1 and 4 h. Moreover we evaluated apoptosis by morphological analysis and caspase-3 activity, also after 24 h. On A549 cells a time-dependent DNA damage, expressed as tail DNA%, beginning from 0.5 microm was found. For oxidative DNA damage an induction after 30 min to 0.5 microm decreasing with time, and a time-dependent increase at 10 microm was found, indicating for low Cr(VI) concentration the oxidative stress as the first event followed by direct DNA damage and for the highest concentration a time-dependent increase in oxidative DNA damage. On BEAS-2B cells DNA damage was induced within 1 h at 0.5-10 microm, without changes with time, showing that BEAS-2B cells are able to resist to Cr(VI) genotoxicity. Early oxidative DNA damage at 0.1 microm decreasing with time was also found. Significant apoptosis was observed by morphological analysis in A549 cells and to a lower extent in BEAS-2B at 10 microm. The exposure to 10 microm induced caspase-3 activity after 4 h in BEAS-2B and after 24 h in A549 cells. The findings show a higher responsiveness of A549 cells to genotoxic effect of Cr(VI) and early transient oxidative DNA damage in BEAS-2B. The results emphasize the suitability of this experimental model to evaluate the early genotoxic response of different cells to non-cytotoxic concentrations of Cr(VI) on target organ.

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Deficient repair of particulate hexavalent chromium-induced DNA double strand breaks leads to neoplastic transformation

Cited by 29 publications

References 28 publications

Chromium and genomic stability

Chromium and genomic stability

Association Between the XRCC6 Polymorphisms and Cancer Risks

Direct‐oxidative DNA damage and apoptosis induction in different human respiratory cells exposed to low concentrations of sodium chromate

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