Metabolic activation and lung toxicity: a basis for cell-selective pulmonary damage by foreign chemicals

The lungs may be exposed to potentially toxic metabolites that are either formed in situ or which are present in the circulation. Therefore, pulmonary injury may be a prominent effect of certain classes of chemicals that undergo bioactivation in the body. The specific types of lung cells damaged may depend upon factors such as preferential exposure or accumulation of parent compounds and/or metabolites, differences in cellular defense mechanisms, or the specific mechanism of activation of the toxicant. Prior knowledge about the metabolism, disposition and mechanism of bioactivation of a particular compound may allow prediction of the type of lung cell damage it is likely to produce. Conversely, morphological observations of characteristic types of cell-specific injury in the lung may suggest a likely biochemical mechanism of toxicity for the particular chemical involved.