Biochemical studies on the toxicity of hematite dust

Biochemical alterations in guinea pig lungs caused by hematite dust were followed at 150 days after intratracheal administration of the dust. In vivo dust exposure caused a significant increase in mitochondrial protein content and cytochrome c oxidase activity whereas diaphorase activity remained unaltered. Mitochondria from the exposed animals were apparently in a swollen state and their contraction profile upon the addition of ATP reflected permeability changes. However, in vitro dust caused no significant alterations. Significant increases in glycogen content along with an insignificant decrease in glycogen phosphorylase activity were also observed in hematite-treated guinea pig lungs. Decrease in drug-metabolizing enzymes such as aniline hydroxylase and tyrosine aminotransferase activities were also evident in the postmitochondrial fraction of the siderotic lungs. [3H]Leucine-incorporation studies showed increased protein synthesis in the postmitochondrial fraction. Increase in protein synthesis in mitochondria was only marginal whereas in whole homogenate it decreased considerably. Experiments employing dust tagged with radioactive iron indicated the rapid mobilization of iron from lung and its distribution to various organs. The presence of iron-binding protein was confirmed by employing Sephadex gel-filtration techniques.