{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T15:25:47Z","timestamp":1790436347850,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,3,21]],"date-time":"2020-03-21T00:00:00Z","timestamp":1584748800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP17H04064 and JP19H05462"],"award-info":[{"award-number":["JP17H04064 and JP19H05462"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP25860292"],"award-info":[{"award-number":["JP25860292"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The onset of malignant mesothelioma (MM) is linked to exposure to asbestos fibers. Asbestos fibers are classified as serpentine (chrysotile) or amphibole, which includes the crocidolite, amosite, anthophyllite, tremolite, and actinolite types. Although few studies have been undertaken, anthophyllite has been shown to be associated with mesothelioma, and tremolite, a contaminant in talc and chrysotile, is a risk factor for carcinogenicity. Here, after characterizing the length and width of these fibers by scanning electron microscopy, we explored the cytotoxicity induced by tremolite and anthophyllite in cells from an immortalized human mesothelial cell line (MeT5A), murine macrophages (RAW264.7), and in a rat model. Tremolite and short anthophyllite fibers were phagocytosed and localized to vacuoles, whereas the long anthophyllite fibers were caught on the pseudopod of the MeT5A and Raw 264.7 cells, according to transmission electron microscopy. The results from a 2\u2010day time\u2010lapse study revealed that tremolite was engulfed and damaged the MeT5A and RAW264.7 cells, but anthophyllite was not cytotoxic to these cells. Intraperitoneal injection of tremolite in rats induced diffuse serosal thickening, whereas anthophyllite formed focal fibrosis and granulomas on peritoneal serosal surfaces. Furthermore, the loss of C<jats:italic>dkn2a\/2b<\/jats:italic>, which are the most frequently lost foci in human MM, were observed in 8 cases of rat MM (homozygous deletion [5\/8] and loss of heterozygosity [3\/8]) by array\u2010based comparative genomic hybridization techniques. These results indicate that tremolite initiates mesothelial injury and persistently frustrates phagocytes, causing subsequent peritoneal fibrosis and MM. The possible mechanisms of carcinogenicity based on fiber diameter\/length are discussed.<\/jats:p>","DOI":"10.1111\/cas.14358","type":"journal-article","created":{"date-parts":[[2020,2,21]],"date-time":"2020-02-21T07:29:06Z","timestamp":1582270146000},"page":"1180-1192","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Frequent homozygous deletion of <i>Cdkn2a\/2b<\/i> in tremolite\u2010induced malignant mesothelioma in rats"],"prefix":"10.1111","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1054-9403","authenticated-orcid":false,"given":"Yasumasa","family":"Okazaki","sequence":"first","affiliation":[{"name":"Department of Pathology and Biological Responses Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuaki","family":"Misawa","sequence":"additional","affiliation":[{"name":"Department of Pathology and Biological Responses Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Akatsuka","sequence":"additional","affiliation":[{"name":"Department of Pathology and Biological Responses Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihiko","family":"Kohyama","sequence":"additional","affiliation":[{"name":"Faculty of Economics Toyo University Graduate School of Economics Tokyo Japan"},{"name":"National Institute of Occupational Safety and Health Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Sekido","sequence":"additional","affiliation":[{"name":"Division of Cancer Biology Aichi Cancer Center Research Institute Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Division of Molecular Carcinogenesis Nagoya University Graduate School of Medicine Nagoya Japan"},{"name":"Aichi Cancer Center Research Institute Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5757-1109","authenticated-orcid":false,"given":"Shinya","family":"Toyokuni","sequence":"additional","affiliation":[{"name":"Department of Pathology and Biological Responses Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,3,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph15051000"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60152-X"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2018.10.401"},{"key":"e_1_2_7_5_1","first-page":"11","article-title":"Arsenic, metals, fibres, and dusts","volume":"100","author":"IARC 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