Zinc chromate induces chromosome instability and DNA double strand breaks in human lung cells.
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.
Xie
Hong
H
Wise Laboratory of Environmental and Genetic Toxicology, University of Southern Maine, 96 Falmouth St., Portland, ME 04104-9300, USA.
Holmes
Amie L
AL
Young
Jamie L
JL
Qin
Qin
Q
Joyce
Kellie
K
Pelsue
Stephen C
SC
Peng
Cheng
C
Wise
Sandra S
SS
Jeevarajan
Antony S
AS
Wallace
William T
WT
Hammond
Dianne
D
Wise
John Pierce
JP
D064007:Ataxia Telangiectasia Mutated Proteins; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002840:Chromates / Q000633:toxicity*; D043171:Chromosomal Instability; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000076228:MRE11 Homologue Protein; D009153:Mutagens / Q000633:toxicity*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D015854:Up-Regulation; D017967:Zinc Compounds / Q000633:toxicity*
D018797:Cell Cycle Proteins; D002840:Chromates; D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; D009153:Mutagens; D025521:Tumor Suppressor Proteins; D017967:Zinc Compounds; C023616:zinc chromate; D004247:DNA; C576324:ATM protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D000076228:MRE11 Homologue Protein