Biochemical mechanisms in asbestos toxicity.

The alarming hazardous nature of asbestos makes it the foremost among toxic fugitive dusts. The biochemical mechanisms responsible for the diverse biological effects of asbestos, such as fibrosis, asbestos bodies, pleural plaques, respiratory difficulty, cancer, and cytotoxicity, are being studied in this laboratory. As asbestosis progresses in guinea pigs, along with reticulum formation, lysosomal enzymes are released from membrane-bound latent state to active free form, initiating degradative changes. Considerable alterations take place in the pulmonary metabolic machinery. Mitochondria in lung cells were found to be important loci for the toxic effect of asbestos. A profile of mitochondrial activity, in control and asbestotic animals, revealed specific enzymic changes such as increased cytochrome c oxidase during the disease. The functional organization of mitochondria was also altered, since the organelles from asbestotic lungs were swollen as measured by spectrophotometry. Glutamate dehydrogenase activity of mitochondria became exposed in asbestosis. The maleate dehydrogenase shunt which is involved in transport of the redox potential across the membrane was enhanced in cytosol and mitochondria. The involvement of microsomal enzymes in asbestosis was indicated by alterations in glucose-6-phosphatase and tyrosine transaminase and aniline hydroxylase. Changes in the biotransformational capacity of lung, due to asbestos, could be an important aspect in toxicity, especially the carcinogenic effect. Considerable alterations were encountered in the levels of different phospholipids and in mucopolysaccharide constituents. On the basis of the above, the molecular mechanisms in asbestos toxicity are explained as an integrated model. Interactions of dust constituents with those of membranes and the ensuing metabolic adjustments are thus important in the etiology of asbestosis.