Carcinogenic lead chromate induces DNA double-strand breaks in human lung cells
- 作者：Hong Xie ; Sandra S. Wise ; Amie L. Holmes ; Bo Xu ; Timothy P. Wakeman ; Stephen C. Pelsue ; Narendra P. Singh and John Pierce Wise ; Sr.
- 关键词：Hexavalent chromium ; DNA double strand breaks ; ATM ; Smc1 ; Lead chromate
- 刊名：Mutation Research/Genetic Toxicology and Environmental Mutagenesis
- 出版年：2005
- 期刊代码：31_13835718
- 类别：pha
- 出版时间：2005
- 卷：586
- 期：2
- 页码：160-172
- 文件大小：573 K
摘要
Hexavalent chromium (Cr(VI)) is a widespread environmental contaminant and a known human carcinogen, generally causing bronchial cancer. Recent studies have shown that the particulate forms of Cr(VI) are the potent carcinogens. Particulate Cr(VI) is known to induce a spectrum of DNA damage such as DNA single strand breaks, Cr-DNA adducts, DNA-protein crosslinks and chromosomal aberrations. However, particulate Cr(VI)-induced DNA double strand breaks (DSBs) have not been reported. Thus, the aim of this study was to determine if particulate Cr(VI)-induces DSBs in human bronchial cells. Using the single cell gel electrophoresis assay (comet assay), showed that lead chromate-induced concentration dependent increases in DSBs with 0.1, 0.5, 1 and 5 μg/cm2 lead chromate inducing a 20, 50, 67 and 109%relative increase in the tail integrated intensity ratio, respectively. Sodium chromate at concentrations of 1, 2.5 and 5 μM induced 38, 78 and 107%relative increase in the tail integrated intensity ratio, respectively. We also show that genotoxic concentrations of lead chromate activate the ataxia telangiectasia mutated (ATM) protein, which is thought to play a central role in the early stages of DSB detection and controls cellular responses to this damage. The H2A.X protein becomes rapidly phosphorylated on residue serine 139 in cells when DSBs are introduced into the DNA by ionizing radiation. By using immunofluorescence, we found that lead chromate-induced concentration-dependent increases in phosphorylated H2A.X (r-H2A.X) foci formation with 0.1, 0.5, 1, 5 and 10 μg/cm2 lead chromate inducing a relative increase in the number of cells with r-H2A.X foci formation of 43, 51, 115 and 129%, respectively.