Thesis presented June 25, 2018

Abstract:
Nanoparticles being more and more used in consumer products, it poses the problem of their occupational toxicology, both for the general population and for exposed workers. One of the great challenges that occupational toxicology has to face is the one of synergistic effects, including the ones between nanoparticles and other, completely unrelated chemicals. As the number of combinations is almost infinite, they cannot be tested without prior knowledge of the molecular responses of cells to the nanoparticles. In our previous work using copper oxide and zinc oxide nanoparticles, we have demonstrated that proteomics is an adequate approach to provide relevant mechanistic knowledge that can be used to divine cross-toxicities. We are planning to extend this approach to two types of metal oxides nanoparticles, e.g. to iron oxides that are used as medicinal products and as food coloring. The relevance of the whole approach also depends of the cell type that will be used, a not all cell types in the body can be expected to encounter nanoparticles. This is why we will focus our work on macrophages, which are the professional scavengers in the body and thus will be in charge of eliminating and handling nanoparticles. In this context, the project can be described rather simply. Using adequate macrophage cell lines, the nanoparticles useful doses will be determined first. Then a proteomic analysis will be carried out to unravel the molecular responses of macrophages to the nanoparticles of interest. These experiments will allow to highlight pathways that will be tested further. Targeted experiments using both macrophage cell lines and primary macrophages will be carried out to determine which of these pathways are ancillary ones and which are critical ones leading to possible cross-toxicities. Primary macrophages will be used to sort out effects that may be specific to continuous cell lines, but are unfortunately not available in sufficient amounts to carry out the whole approach, especially the proteomic step, and this is why such a combined approach is needed.

Keywords:
nanoparticles, proteomics, cytotoxicity, macrophages

On-line thesis.