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Current Perspectives on Particulate Induced Pulmonary TumoursZENECA Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, SK10 4TJ, UK 1 Chronic exposure to insoluble particulates can lead to the development of pulmonary tumours. These have been classified as broncho-alveolar or squamous/epidermoid according to their histopathological characteristics and have been reported in inhalation studies in rats of materials ranging from diesel exhaust and silica to titanium dioxide. 2 The sequence of changes within the rat lung leading to tumours has been characterised. It is apparent that one prerequisite is that the lung load of the particulate matter must exceed the normal clearance capacity, either by overloading the normal alveolar macrophage mediated mechanism or by induction of toxicity with materials such as silica. This results in inflammatory responses, including, or resulting in, epithelial hypertrophy and/or hyperplasia and squamous metaplasia. The persistence of these tissue responses over chronic time periods can lead to tumorigenesis. 3 Research into the mechanisms involved in the initiation and progression of both the inflammatory response and subsequent tumorigenic response to lung particulate loading is in progress. Impairment of macrophage function and mobility by inert particles constitutes one route by which this can arise, as does toxicity to this cell type by biologically reactive particles. At the molecular level, the role of inflammatory mediators, especially the cytokines, has received much attention. 4 Particulate induced lung tumours are perceived to be a phenomenon specific to the rat and their relevance to man is questionable.
Human & Experimental Toxicology, Vol. 13, No. 10,
700-715 (1994) |
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