Asbestos surface provides a niche for oxidative modification

Asbestos is a potent carcinogen associated with increased risks of malignant mesothelioma and lung cancer in humans. Although the mechanism of carcinogenesis remains elusive, the physicochemical characteristics of asbestos play a role in the progression of asbestos‐induced diseases. Among these characteristics, a high capacity to adsorb and accommodate biomolecules on its abundant surface area has been linked to cellular and genetic toxicity. Several previous studies identified asbestos‐interacting proteins. Here, with the use of matrix‐assisted laser desorption ionization‐time of flight mass spectrometry, we systematically identified proteins from various lysates that adsorbed to the surface of commercially used asbestos and classified them into the following groups: chromatin/nucleotide/RNA‐binding proteins, ribosomal proteins, cytoprotective proteins, cytoskeleton‐associated proteins, histones and hemoglobin. The surfaces of crocidolite and amosite, two iron‐rich types of asbestos, caused more protein scissions and oxidative modifications than that of chrysotile by in situ‐generated 4‐hydroxy‐2‐nonenal. In contrast, we confirmed the intense hemolytic activity of chrysotile and found that hemoglobin attached to chrysotile, but not silica, can work as a catalyst to induce oxidative DNA damage. This process generates 8‐hydroxy‐2′‐deoxyguanosine and thus corroborates the involvement of iron in the carcinogenicity of chrysotile. This evidence demonstrates that all three types of asbestos adsorb DNA and specific proteins, providing a niche for oxidative modification via catalytic iron. Therefore, considering the affinity of asbestos for histones/DNA and the internalization of asbestos into mesothelial cells, our results suggest a novel hypothetical mechanism causing genetic alterations during asbestos‐induced carcinogenesis. (Cancer Sci 2011; 102: 2118–2125)