{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T09:36:09Z","timestamp":1785317769501,"version":"3.55.0"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"vor","delay-in-days":27,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"JSPS Kakenhi","award":["JP20H05502"],"award-info":[{"award-number":["JP20H05502"]}]},{"name":"JSPS Kakenhi","award":["JP19H05462"],"award-info":[{"award-number":["JP19H05462"]}]},{"name":"JST CREST","award":["JPMJCR19H4"],"award-info":[{"award-number":["JPMJCR19H4"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Objectives: The natural fibrous mineral, asbestos, has been useful in industry for many centuries. In the 1960s, epidemiology recognized the association between asbestos exposure and mesothelioma, and in 1987 the International Agency for Research on Cancer designated all kinds of asbestos as Group 1 carcinogens. However, various scientific enigmas remained regarding the molecular mechanisms of asbestos-induced mesothelial carcinogenesis. This review article was undertaken to reveal and summarize recent discoveries to resolve those enigmas.<\/jats:p>\n               <jats:p>Methods: We collected recent important findings from our own laboratory and others to explain why mesothelial cells are the target for asbestos-induced carcinogenesis and what are the key molecular mechanisms.<\/jats:p>\n               <jats:p>Results: The long incubation period of 30-40\u00a0years for mesothelial carcinogenesis after asbestos exposure allows the asbestos fibers to go through the pulmonary parenchyma from the central to peripheral portions and ultimately reach the parietal mesothelium by piercing visceral pleura. Asbestos fibers have affinity for hemoglobin and histones, thus accumulating iron on the surface while traveling through the lung. Mesothelial cells are phagocytic cells, engulfing iron-coated asbestos fibers. Accordingly, homozygous deletion of the p16INK4a tumor suppressor gene, a signature of excess iron-induced carcinogenesis, is acquired through oxidative DNA damage. Recently, exosome-dependent iron transfer from asbestos-fed macrophages to mesothelial cells was reported. Similar molecular mechanisms are observed with multiwalled carbon nanotubes of ~50-nm diameter.<\/jats:p>\n               <jats:p>Conclusions: Physical dimensions, biopersistence, and affinity to iron\/histones are essential for fibrous material to be carcinogenic to mesothelial cells. Therefore, local iron reduction may be a strategy to prevent mesothelial carcinogenesis.<\/jats:p>","DOI":"10.1093\/joccuh\/uiae064","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T04:37:40Z","timestamp":1738039060000},"source":"Crossref","is-referenced-by-count":3,"title":["Decoding the molecular enigma behind asbestos and fibrous nanomaterial-induced carcinogenesis"],"prefix":"10.1093","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5757-1109","authenticated-orcid":false,"given":"Shinya","family":"Toyokuni","sequence":"first","affiliation":[{"name":"Nagoya University Graduate School of Medicine Department of Pathology and Biological Responses, , 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550,","place":["Japan"]},{"name":"Nagoya University Center for Low-temperature Plasma Sciences, , Furo-cho, Chikusa-ku, Nagoya 464-8603,","place":["Japan"]},{"name":"Tokai National Higher Education and Research System Center for Integrated Sciences 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