title: Asbestos surface provides a niche for oxidative modification.
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.
authors: Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Hirotaka
authors: H
authors: Nagai
authors: Toshikazu
authors: T
authors: Ishihara
authors: Wen-Hua
authors: WH
authors: Lee
authors: Hiroki
authors: H
authors: Ohara
authors: Yasumasa
authors: Y
authors: Okazaki
authors: Katsuya
authors: K
authors: Okawa
authors: Shinya
authors: S
authors: Toyokuni
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D017639:Asbestos, Amosite / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D017638:Asbestos, Crocidolite / Q000737:chemistry* / Q000633:toxicity; D017632:Asbestos, Serpentine / Q000737:chemistry* / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000096:biosynthesis; D006454:Hemoglobins / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D008175:Lung Neoplasms / Q000209:etiology / Q000473:pathology; D008654:Mesothelioma / Q000209:etiology / Q000473:pathology; D051379:Mice; D010084:Oxidation-Reduction; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D012269:Ribosomal Proteins / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013499:Surface Properties
chemical_list: D000447:Aldehydes; D017632:Asbestos, Serpentine; D002843:Chromatin; D006454:Hemoglobins; D006657:Histones; D011506:Proteins; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D017638:Asbestos, Crocidolite; D017639:Asbestos, Amosite; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D007501:Iron; D003849:Deoxyguanosine; C027576:4-hydroxy-2-nonenal