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Transcriptional signatures and potential biomarkers of asphalt fume exposure in rat epithelial cells using DNA microarrays.
Keshava-C; Keshava-N; Law-BF; Weston-A
Environ Mol Mutagen 2006 Jul; 47(6):418
Exposure to asphalt fume occurs during paving and roofing operations. Occupational exposure to asphalt fume may pose a health risk to workers. The exact chemical composition of asphalt fume depends on the chemical complexity of the original crude petroleum, the manufacturing process, and the temperature at which the asphalt is applied. Nevertheless, asphalt fume consists mainly of aliphatic compounds, cyclic alkanes, cyclic aromatic hydrocarbons, and heterocyclic compounds. Most studies to date have focused on the biological effect of asphalt fume with emphasis on carcinogenic polycyclic aromatic hydrocarbon content identification of molecular signatures associated with the biological processes that underlie chemical carcinogenesis may assist in the evaluation of carcinogenic potentials of various chemicals and complex chemical mixtures. Since asphalt generates a mixture of potentially carcinogenic chemicals, this study investigates the effects of asphalt fume condensate on gene expression in rat lung epithelial cells in order to identify potential exposure biomarkers. Transcription was monitored in rat epithelial cells (alveolar type II, RLE-6TN) in response to asphalt fume exposure (12 or 24H) using rat genome U34A microarrays (Affymetrix) with 8800 total genes. Transcripts were detected for 42% of the genes, of these, 348 were altered by at least 2 fold at either 12 or 24h. Genes altered at both time points included cell cycle control genes (cyclin B1 and D3); transcription factors (TCFE2a, ATF3) and DNA damage response genes (GADD45, GADD153). Also, carcinogen metabolism genes, CVP1A1, CVP1B1, GSTs, ALDH, NQO1 were induced (P<0.01) at both time points. Expression profiles of representative genes (phase I and phase II metabolism, DNA repair and cell cycle genes) were confirmed using real-time polymerase chain reaction. Here, we report the identification of a battery of genes altered by exposure to asphalt fume condensate in rat epithelia cells. These data suggest potential biomarkers of asphalt fume condensate exposure and may provide insights into a potential molecular mechanism of asphalt fume condensate-induced carcinogenesis.
Dosimetry; Lung; Models; Animals; Animal-studies; Risk-analysis; Laboratory-animals; Quantitative-analysis; Chronic-exposure; Lung-cancer; Cancer; Lung-burden; Pulmonary-system-disorders
Issue of Publication
Environmental and Molecular Mutagenesis