Alterations in collagen biosynthesis and in metallothionein in lungs of rats acutely or repeatedly exposed to cadmium chloride aerosol.

Comparisons were made between morphologic and biochemical changes occurring in the lungs of rats receiving a single exposure or repeated 2-h exposures of aerosolized 0.1% cadmium chloride, simulating varied exposure conditions potentially experienced by humans. Lung lysyl oxidase activity increases in both models, although less so with repeated exposures. Pulsing lung tissue in vitro with 3H-proline indicated that rates of collagen biosynthesis were elevated preferentially over rates of noncollagen protein synthesis in both exposure models. Lung metallothionein increased nearly linearly over 21 days of repeated exposure. Histologic examination revealed scarred lesions distorting alveolar structure and bronchioles in both models. However, scarring and cell exudation into the airways and interstitium was less in the repeatedly exposed model. The results indicate the activation of a connective tissue repair reaction in both models. Increased levels of metallothionein after repeated exposure may both sequester cadmium and reduce pools of copper available for lysyl oxidase synthesis, thus limiting the fibrotic response.