Evaluation of the effect of hard metal on the gene expression in human peripheral blood mononucleated cells, human primary monocytes and the human aveolar epithelial cell line A549.

The mechanisms for lung fibrosis versus cancer induction by hard metal (WC-Co) are not yet clearly understood. While the asthmatic responses are caused by cobalt species, the development of cancer and fibrosing alveolitis is mainly ascribed to the simultaneous exposure to cobalt and tungsten carbide particles. In vitro in human PBMC and in vivo in rat pneumocytes, it has been shown that WC-Co is inducing genotoxicity and apoptosis.
The objective of this project is to compare the expression levels of different classes of genes involved in apoptosis, cell proliferation, inflammation, cell cycle control and DNA repair in relevant human cell types: peripheral blood mononucleated cells (reporter cells for biomonitoring), primary monocytes and alveolar epithelial cells A549 (target cells for cancer inducing effects on the lung) treated with hard metal (WC-Co). This gene expression analysis will be situated on 2 levels: 1) on mRNA level (transcriptomics) with micro-arrays and 2) on protein level (proteomics) with ELISAs to have a quantitative idea about the relevant up/down regulated genes demonstrated on mRNA level. A better knowledge of these different signalization pathways would give a better understanding about the modulating effects of apoptosis (elimination of mutated cells, indirect stimulation of cell proliferation) on the induction of fibrosis and lung cancer.