Respiratory tract carcinogenesis by mineral fibres and dusts: models and mechanisms.

Experimental pathology studies in respiratory carcinogenesis by mineral fibres and dusts are reviewed. Animal models, analogous to the corresponding human pathology, were developed for carcinogenesis by polycyclic aromatic hydrocarbons carried on mineral particles, by N-nitroso compounds, by asbestos fibres and by crystalline silica (quartz). Species and organ susceptibility factors determine marked differences in the carcinogenic response to silica in different species and target organs, suggesting possible pathogenetic mechanisms, such as the role of surface oxygen radicals and the induction of related enzymes. Cellular models have been effectively used to study the induction of toxicity and neoplastic transformation by mineral fibres and dusts. Cell culture models have been developed for respiratory epithelial cells and for their transformation. These include not only models for the laryngotracheobronchial columnar epithelium, but also for the alveolar type II epithelium and its transformation by silica. Recent studies on simian virus (SV)40 carcinogenesis in animal and cellular models and on the detection of SV40-like sequences in the deoxyribonucleic acid of human tumours point to the need for much further research on the role of interactions of viral, chemical and physical factors in human respiratory carcinogenesis.