The mitochondrial activation of silicate and its role in silicosis, black lung disease and lung cancer.

Silicate substitutes for phosphate in the transitory uncoupling of rat liver mitochondria induced by hydrazine when beta-hydroxy-butyrate is the substrate. Uncoupling is blocked by rutamycin. Just as in the case when phosphate is combined with hydrazine, ATP, ADP, PPi, and Mg++ protect against hydrazine when silicate is combined with hydrazine. A high level of ADP in the absence of added phosphate, but in the presence of silicate, induces a pseudo state three of the mitochondria. Silicate, like sulfate and arsenate which have been reported previously, is activated by the enzymes which mediate oxidative phosphorylation. These results serve to explain a role for silicate in silicosis, black lung disease, and cancer. In addition, since there is suggestive evidence in the literature that lung tissue solubilizes asbestos fibers, these results not only expand the confluence between oxidative phosphorylation and chemical carcinogenesis but are correlated with the synergistic carcinogenicity of asbestos and smoking observed by epidemiologists.