Document Detail


Gene profiling of normal human bronchial epithelial cells in response to asbestos and benzo(a)pyrene diol epoxide (BPDE).
MedLine Citation:
PMID:  18197826     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Asbestos and benzo(a)pyrene diol epoxide (BPDE) are pulmonary carcinogens with synergistic interaction in causing lung cancer. We used Affymetrix microarrays to study gene modulation in vitro using normal human bronchial epithelial cells exposed to chrysotile asbestos and/or BPDE for 4 or 24 h. Linear models were used to compare treated cells to controls at each time point to identify statistically significant up- or downregulation of genes. Profiles of genes regulated by chrysotile were dominated by cytokines, growth factors, and DNA damage. Profiles of genes with BPDE and chrysotile regulation were correlated with proliferation, DNA damage recognition and nucleotide-excision repair, cytokines, and apoptosis. Chemokines, growth-regulated oncogene-alpha (Gro-alpha, CXCL-1), and IL-8, were significantly increased, and these had previously been observed in bronchoalveolar lavage from asbestos workers or in animal models. Interestingly, the Hermansky-Pudlak gene, which is mutated in an autosomal recessive form of pulmonary fibrosis, was downregulated threefold by BPDE at 4 h. This is an interesting example of gene (Hermansky-Pudlak syndrome) and environment (BPDE) interaction. Transcription factors, including activating transcription factor 3 and Cbp/p300-interacting transactivator, were upregulated by chrysotile. Real Time PCR for IL-8, ATF-3, GADD45B, CXC Ligand 1, and CTGF compared to GAPDH validated microarray findings at 24 h. These in vitro findings in NHBE cells model environment-gene interaction for asbestos and BPDE, highlighting effects of inflammation, fibrosis, proliferation, and DNA damage recognition and repair.
Authors:
Ilana Belitskaya-Levy; Mustapha Hajjou; Wei-cheng Su; Ting-An Yie; Kam-Meng Tchou-Wong; Moon-shong Tang; Judith D Goldberg; William N Rom
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer     Volume:  26     ISSN:  0731-8898     ISO Abbreviation:  J. Environ. Pathol. Toxicol. Oncol.     Publication Date:  2007  
Date Detail:
Created Date:  2008-01-16     Completed Date:  2008-03-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8501420     Medline TA:  J Environ Pathol Toxicol Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  281-94     Citation Subset:  IM    
Affiliation:
Division of Biostatistics, Department of Environmental Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
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MeSH Terms
Descriptor/Qualifier:
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / toxicity*
Asbestos, Serpentine / toxicity*
Bronchi / cytology,  drug effects*,  metabolism
Cells, Cultured
Down-Regulation
Drug Synergism
Epithelial Cells / drug effects*,  metabolism
Gene Expression / drug effects*
Gene Expression Profiling*
Humans
Oligonucleotide Array Sequence Analysis
Reverse Transcriptase Polymerase Chain Reaction
Up-Regulation
Grant Support
ID/Acronym/Agency:
ES 007267/ES/NIEHS NIH HHS; M01 RR00096/RR/NCRR NIH HHS; P30 CA16087/CA/NCI NIH HHS; P30 ES00260/ES/NIEHS NIH HHS; U01 CA86137/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Asbestos, Serpentine; 55097-80-8/7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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