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Journal of Environmental Pathology, Toxicology and Oncology
Facteur d'impact: 1.241 Facteur d'impact sur 5 ans: 1.349 SJR: 0.356 SNIP: 0.613 CiteScore™: 1.61

ISSN Imprimer: 0731-8898
ISSN En ligne: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.v26.i4.50
pages 281-294

Gene Profiling of Normal Human Bronchial Epithelial Cells in Response to Asbestos and Benzo(a)pyrene diol epoxide (BPDE)

Ilana Belitskaya-Levy
Division of Biostatistics, and Department of Environmental Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
Mustapha Hajjou
Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
Wei-cheng Su
Department of Environmental Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
Ting-An Yie
Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
Kam-Meng Tchou-Wong
Division of Pulmonary and Critical Care Medicine, and Department of Environmental Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
Moon-shong Tang
Department of Environmental Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
Judith D. Goldberg
Departments of Pathology and Environmental Medicine, and Division of Pulmonary and Critical Care Medicine. NYU School of Medicine, New York, NY 10016
William N. Rom
Division of Pulmonary and Critical Care Medicine, and Department of Environmental Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA

RÉSUMÉ

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-α, 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.


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