Signal transduction pathways relevant for neoplastic effects of fibrous and non-fibrous particles.

Apart from their genotoxic effects, both fibrous and non-fibrous particles are known to induce signalling pathways involved in the development of malignant lung diseases. Different direct effects of particles as well as indirect cellular effects are believed to induce changes in apoptosis or proliferation in target cells. Signalling events, e.g. the induction of mitogen-activated protein kinase (MAPK) cascades resulting in the activation of the transcription factor AP-1, as well as the induction of the transcription factor NFkappaB which mainly mediates the expression of pro-inflammatory genes are discussed. There is some insight into the molecular mechanisms eliciting these pathways. Therefore, this review aims to give an overview on signalling pathways as well as initial events including effects of reactive oxygen and nitrogen species, membrane receptors and particle uptake.