Zinc chromate induces chromosome instability and DNA double strand breaks in human lung cells

被引:43
作者
Xie, Hong [1 ,2 ,3 ]
Holmes, Amie L. [1 ,2 ,3 ]
Young, Jamie L. [1 ,2 ,3 ]
Qin, Qin [1 ,2 ,3 ]
Joyce, Kellie [1 ,2 ]
Pelsue, Stephen C. [3 ]
Peng, Cheng [4 ]
Wise, Sandra S. [1 ]
Jeevarajan, Antony S. [5 ]
Wallace, William T. [5 ]
Hammond, Dianne [5 ]
Wise, John Pierce, Sr. [1 ,2 ,3 ]
机构
[1] Univ So Maine, Wise Lab Environm & Genet Toxicol, Portland, ME 04104 USA
[2] Univ So Maine, Maine Ctr Toxicol & Environm Hlth, Portland, ME 04104 USA
[3] Univ So Maine, Dept Appl Sci Med, Portland, ME 04103 USA
[4] Univ So Maine, Dept Math & Stat, Portland, ME 04103 USA
[5] Lyndon B Johnson Space Ctr, Houston, TX 77058 USA
关键词
Chromium; Zinc chromate; Chromosome instability; DNA double strand breaks; HUMAN BRONCHIAL CELLS; S-PHASE CHECKPOINT; SOLUBLE HEXAVALENT CHROMIUM; BASE EXCISION-REPAIR; LEAD CHROMATE; CANCER MORTALITY; NEOPLASTIC TRANSFORMATION; EPITHELIAL-CELLS; CHRONIC EXPOSURE; MISMATCH REPAIR;
D O I
10.1016/j.taap.2008.10.010
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Hexavalent chromium Cr(VI) is a respiratory toxicant and carcinogen, with Solubility playing an important role in its carcinogenic potential. Zinc chromate, a water insoluble or 'particulate' Cr(VI) compound, has been shown to be carcinogenic in epidemiology studies and to induce tumors in experimental animals, but its genotoxicity is poorly understood. Our study shows that zinc chromate induced concentration-dependent increases in cytotoxicity, chromosome damage and DNA double strand breaks in human lung cells. In response to zinc chromate-induced breaks, MRE11 expression was increased and ATM and ATR were phosphorylated, indicating that the DNA double strand break repair system was initiated in the cells. In addition, our data show that zinc chromate-induced double strand breaks were only observed in the G2/M phase population, with no significant amount of double strand breaks observed in G1 and S phase cells. These data will aid in understanding the mechanisms of zinc chromate toxicity and carcinogenesis. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:293 / 299
页数:7
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