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Journal of Environmental Pathology, Toxicology and Oncology

ISSN for PRINT: 0731-8898

Institutional price:	$672.00
Issues per year:	4

Best Paper Award Selection - Editorial Board Site

2007, Volume26

89 pages

Issue price - $187.00

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
Division of Biostatistics, and Department of Environmental Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA

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

ABSTRACT

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.