Iron In Asbestos-induced Cancer
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Iron In Asbestos-induced Cancer
Asbestos surface provides a niche for oxidative modification.
Cancer Sci. 2011 Sep 2.
Nagai H, Ishihara T, Lee WH, Ohara H, Okazaki Y, Okawa K, Toyokuni S.
Department of Pathology and Biological Responses, Nagoya University
Graduate School of Medicine, Nagoya, 466-8550,
Japan Department of Pathology and Biology of Diseases, Kyoto
University Graduate School of Medicine, Kyoto, 606-8501,
Japan Biomolecular Characterization Unit, Horizontal Medical Research
Organization, Kyoto University Graduate School of Medicine, Kyoto,
606-8501, Japan.
Abstract
Asbestos is a potent carcinogen associated with increased risks of
malignant mesothelioma and lung cancer in humans.
Though 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, by the use of matrix-assisted laser desorption ionization-time
of flight mass spectrometry (MALDI-TOF/MS), 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. On
the other hand, 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.
© 2011 Japanese Cancer Association.
PMID:21895868
doi: 10.1111/j.1349-7006.2011.02087.x.
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