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Airborne particulate collected from central Taiwan induces DNA strand breaks, Poly(ADP-ribose) polymerase-1 activation, and estrogen-disrupting activity in human breast carcinoma cell lines.
MedLine Citation:
PMID:  23043339     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
The objectives of this investigation were to examine whether airborne particles induce DNA damaging and estrogen-disrupting effects and to explore the relationships between them. In this study, airborne particulate was collected at an urban, a suburban, and a rural site in central Taiwan. The organic solvent extracts of airborne particulate were examined in human MCF-7 and T47D-KBluc breast cancer cells. We observed significant increases in reactive oxygen species (ROS) generation in MCF-7 cells after treatment with the particulate extracts whereas aryl hydrocarbon receptor (AhR) antagonist blocked the particulate-induced ROS generation in cells. Further, induction of CYP1A1 protein expression was confirmed by immunoblots in cells treated with airborne particles, suggesting the roles of AhR status in mediating the particulate-induced toxicity. In addition, we observed that at non-cytotoxic concentration (∼0.01 m(3) air equivalent), airborne particles induced decreases in intracellular NAD(P)H and NAD(+) in MCF-7 cells. These decreases were completely blocked by three types of poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors. Moreover, we demonstrated increases in the number of DNA strand breaks in MCF-7 cells exposed to airborne particles as measured by the single-cell gel electrophoresis (Comet) assay. Overall, this evidence confirms that airborne particles induce decreases in intracellular NAD(P)H and NAD(+) through PARP-1 activation mediated by formation of DNA strand breaks. Furthermore, we confirmed that with series dilution airborne particles (∼10(-7)-10(-2) m(3) air equivalent) possess both estrogenic and anti-estrogenic activities as determined by the ERα-mediated reporter gene assay in human T47D-KBluc breast cancer cells. In conclusions, we confirmed that the DNA-damaging activity and estrogenicity of airborne particles varied considerably with concentration (air equivalent). Our findings add further support to the theme that ROS formation is a significant determinant factor in mediating the induction of oxidative DNA damage and repair in human breast cancer cells exposed to airborne particles and that oxidative stress and the subsequent induction of DNA damage may, in part, contribute to airborne particle-induced carcinogenesis.
Authors:
Shou-Tung Chen; Chia-Chi Lin; Yi-Shiau Liu; Che Lin; Pei-Tzu Hung; Chia-Wen Jao; Po-Hsiung Lin
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of environmental science and health. Part A, Toxic/hazardous substances & environmental engineering     Volume:  48     ISSN:  1532-4117     ISO Abbreviation:  J Environ Sci Health A Tox Hazard Subst Environ Eng     Publication Date:  2013  
Date Detail:
Created Date:  2012-10-09     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9812551     Medline TA:  J Environ Sci Health A Tox Hazard Subst Environ Eng     Country:  England    
Other Details:
Languages:  eng     Pagination:  173-81     Citation Subset:  IM    
Affiliation:
a Changhua Christian Hospital, Comprehensive Breast Cancer Center , Changhua , Taiwan.
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