Asbestos surface provides a niche for oxidative modification

Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Cancer Science (Impact Factor: 3.52). 09/2011; 102(12):2118-25. DOI: 10.1111/j.1349-7006.2011.02087.x
Source: PubMed

ABSTRACT 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.

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Available from: Shinya Toyokuni, Sep 22, 2014
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    • "However, surprisingly, human mesothelioma was the second most similar. It is now established that most human mesothelioma results from exposure to asbestos, and the primary pathogenic process involved is iron overload [8], [61]. The same mesodermal origin of renal tubular cells and mesothelial cells may cause the similarity of the array-based CGH profiles. "
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