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Communication Dans Un Congrès Année : 2009

Identification of genes regulated by the environmental contaminant benzo(a)pyrene in primary human macrophages

Résumé

Polycyclic aromatic hydrocarbons (PAHs), such as benzo(a)pyrene (BP) are ubiquitous environmental contaminants generated by a variety of industrial processes. They exert a wide range of toxic effects including inflammation and carcinogenesis which have been linked, at least in part, to activation of the aryl hydrocarbon receptor (AhR), a ligand-activated basic helix-loop-helix transcriptional factor and to the formation of DNA adducts. Moreover, we have demonstrated that exposure to BP inhibits the differentiation of human monocytes into macrophages and that mature differentiated macrophagic cells also constitute targets for BP. However, the molecular basis of this PAH-induced immunotoxicity is poorly understood. In this way, a precise identification by microarrays of genes regulated by aromatic hydrocarbons is likely interesting to perform in order to characterize molecular targets of PAHs. Moreover, whereas several microarray-based gene expression studies have been conducted to investigate the mechanism of PAH toxicity in various cell strains or tissues of human or rodent origin, only few of these studies have been conducted in human normal cells and especially no study has been done in human macrophagic cells. By using microarray (pangenomic chips 44K Agilent), we have identified a set of genes that are regulated by BP in primary human macrophages. We then attempted to confirm array findings for the leading differentially expressed genes, using real-time quantitative polymerase chain reaction (RT-qPCR). Preliminary data indicate the identification of genes directly regulated by the AhR and also of genes whose regulation are rather linked to the formation of DNA adducts. Such genes may represent potential biomarkers of PAHs-exposure or effects in normal human cells, which could be useful in molecular epidemiology and risk evaluation.

Domaines

Cancer
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Dates et versions

hal-00673940 , version 1 (24-02-2012)

Identifiants

  • HAL Id : hal-00673940 , version 1

Citer

Lydie Sparfel, Marie-Laure Pinel-Marie, Magali Boize, Serge Koscielny, Sophie Desmots, et al.. Identification of genes regulated by the environmental contaminant benzo(a)pyrene in primary human macrophages. Annual Meeting 100th American Association for Cancer Research, Apr 2009, Denver, United States. ⟨hal-00673940⟩
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