Distinct cytoskeletal injuries induced by As, Cd, Co, Cr, and Ni compounds

The risks of metal compounds to human health are highlighted by the ubiquity of exposure and their persistence in the environment. Although compounds of As, Cd, Co, Cr, and Ni are known or "reasonably anticipated" to be carcinogenic to humans and/or experimental animals, the cellular targets of these health hazards and the underlying mechanisms of their carcinogenicity are still unclear. We show in this report that dramatic, time- and dose-dependent cytoskeletal perturbations, especially in the distribution and organization patterns of microtubules and microfilaments, two of the principal components of the cytoskeleton, occurred in 3T3 cells upon exposure to these metal salts. Each metal salt appeared to induce a different, typical pattern of cytoskeletal injury, probably reflecting the specificity of action of each metal ion. These results suggest that the cytoskeleton can indeed act as a target for injury by epigenetic carcinogenic metal compounds in the environment. These findings should help our efforts to understand the mechanisms of action of metal compounds at the subcellular and molecular levels.