The main objective of this project is to use dendritic-like cells derived from a human cell line to develop a robust in vitro system to distinguish between respiratory vs contact sensitising chemicals. Whilst the use of cell lines will help to circumvent the problem of donor variation other aspects of their use will also need to be defined. The objective will be to establish the optimal conditions to obtain appropriate differentiation (as immature dendritic cells) of the KG-1 and MUTZ-3 cell lines. To establish the suitable conditions for in vitro challenge by respiratory and contact sensitising chemicals (both breakdown and metabolism). To challenge immature dendritic cells with the dinitrochlorobenzene (DNCB) and p-phenylenediamine (PPDA) contact sensitisers and toluene diisocyanate (TDI) and trimetallic anhydrides (TMA). To compare these two types of sensitising chemicals on the differentiation, cytokine expression, and immune function of dendritic cells. To use one cell line to assess a wide range of respiratory vs contact sensitising chemicals. To demonstrate that chemical induced changes in dentritic cells could form the basis of a robust method to identify chemicals that have the ability to cause sensitization of the respiratory tract.
RELATED TO THE PROJECT:
Van Sittert N. J., Boogaard P. J., Natarajan A. T., Tates A. D., Ehrenberg L. G., Tornqvist M. A., Comparative analysis of induced mutations in the cytoplasmic and nuclear genome (Tenovus Cancer Charity), Mut. Res., 447, 2000, pp. 27-48. Final report and publications expected for 2005.