Yasushi Shinohara
National Institute of Occupational Health
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Yasushi Shinohara.
Cancer Science | 2008
Li Jiang; Hirotaka Nagai; Hiroki Ohara; Shigeo Hara; Mitsuhiro Tachibana; Seishiro Hirano; Yasushi Shinohara; Norihiko Kohyama; Shinya Akatsuka; Shinya Toyokuni
Respiratory exposure to asbestos has been linked with mesothelioma in humans. However, its carcinogenic mechanism is still unclear. Here we studied the ability of chrysotile, crocidolite and amosite fibers to induce oxidative DNA damage and the modifying factors using four distinct approaches. Electron spin resonance analyses revealed that crocidolite and amosite containing high amounts of iron, but not chrysotile, catalyzed hydroxyl radical generation in the presence of H2O2, which was enhanced by an iron chelator, nitrilotriacetic acid, and suppressed by desferal. Natural iron chelators, such as citrate, adenosine 5′‐triphosphate and guanosine 5′‐triphosphate, did not inhibit this reaction. Second, we used time‐lapse video microscopy to evaluate how cells cope with asbestos fibers. RAW264.7 cells, MeT‐5 A and HeLa cells engulfed asbestos fibers, which reached not only cytoplasm but also the nucleus. Third, we utilized supercoiled plasmid DNA to evaluate the ability of each asbestos to induce DNA double strand breaks (DSB). Crocidolite and amosite, but not chrysotile, induced DNA DSB in the presence of iron chelators. We cloned the fragments to identify break sites. DSB occurred preferentially within repeat sequences and between two G:C sequences. Finally, i.p. administration of each asbestos to rats induced not only formation of nuclear 8‐hydroxy‐2′‐deoxyguanosine in the mesothelia, spleen, liver and kidney but also significant iron deposits in the spleen. Together with the established carcinogenicity of i.p. chrysotile, our data suggest that asbestos‐associated catalytic iron, whether constitutional or induced by other mechanisms, plays an important role in asbestos‐induced carcinogenesis and that chemoprevention may be possible through targeting the catalytic iron. (Cancer Sci 2008; 99: 2142–2151)
The Journal of Pathology | 2012
Li Jiang; Shinya Akatsuka; Hirotaka Nagai; Shan-Hwu Chew; Hiroki Ohara; Yasumasa Okazaki; Yoriko Yamashita; Yutaka Yoshikawa; Hiroyuki Yasui; Katsuya Ikuta; Katsunori Sasaki; Yutaka Kohgo; Seishiro Hirano; Yasushi Shinohara; Norihiko Kohyama; Takashi Takahashi; Shinya Toyokuni
Exposure to asbestos is a risk for malignant mesothelioma (MM) in humans. Among the commercially used types of asbestos (chrysotile, crocidolite, and amosite), the carcinogenicity of chrysotile is not fully appreciated. Here, we show that all three asbestos types similarly induced MM in the rat peritoneal cavity and that chrysotile caused the earliest mesothelioma development with a high fraction of sarcomatoid histology. The pathogenesis of chrysotile‐induced mesothelial carcinogenesis was closely associated with iron overload: repeated administration of an iron chelator, nitrilotriacetic acid, which promotes the Fenton reaction, significantly reduced the period required for carcinogenesis; massive iron deposition was found in the peritoneal organs with high serum ferritin; and homozygous deletion of the CDKN2A/2B/ARF tumour suppressor genes, the most frequent genomic alteration in human MM and in iron‐induced rodent carcinogenesis, was observed in 92.6% of the cases studied with array‐based comparative genomic hybridization. The induced rat MM cells revealed high expression of mesoderm‐specific transcription factors, Dlx5 and Hand1, and showed an iron regulatory profile of active iron uptake and utilization. These data indicate that chrysotile is a strong carcinogen when exposed to mesothelia, acting through the induction of local iron overload. Therefore, an intervention to remove local excess iron might be a strategy to prevent MM after asbestos exposure. Copyright
American Journal of Industrial Medicine | 2015
Zhibin Gao; Kenzo Hiroshima; Xiaodong Wu; Jixian Zhang; Dichu Shao; Huajiang Shao; Hanqing Yang; Toshikazu Yusa; Takako Kiyokawa; Makio Kobayashi; Yasushi Shinohara; Oluf Dimitri Røe; Xing Zhang; Kenji Morinaga
BACKGROUND Chrysotile had been used in asbestos textile workshops in Southeast China but a clear relation to mesothelioma is lacking. METHODS All patients diagnosed with mesothelioma from 2003 to 2010 at Yuyao Peoples Hospital were re-evaluated by multiple expert pathologists with immunohistochemistry and asbestos exposure data were collected. RESULTS Of 43 patients with a mesothelioma diagnosis, 19 peritoneal and nine pleural cases were finally diagnosed as mesothelioma. All were females, and the mean age of the patients with peritoneal or pleural mesothelioma was 52.4 and 58.2 years, respectively. All these cases had a history of domestic or occupational exposure to chrysotile. Two-thirds of the patients were from two adjoining towns with multiple small asbestos textile workshops. Contamination of tremolite was estimated to be less than 0.3%. CONCLUSIONS This is a report of mesothelioma in women exposed to chrysotile asbestos at home and at work, with an over-representation of peritoneal mesothelioma.
Industrial Health | 2004
Yasushi Shinohara; Norihiko Kohyama
Industrial Health | 2006
Mitsutoshi Takaya; Yasushi Shinohara; Fumio Serita; Mariko Ono-Ogasawara; Noriko Otaki; Tadao Toya; Ayako Takata; Katsumi Yoshida; Norihiko Kohyama
Sangyo Eiseigaku Zasshi | 2010
Mitsutoshi Takaya; Fumio Serita; Mariko Ono-Ogasawara; Yasushi Shinohara; Hiroyuki Saito; Shigeki Koda
Industrial Health | 1993
Yasushi Shinohara
Industrial Health | 1996
Yasushi Shinohara
Journal of The Sedimentological Society of Japan | 2000
Saburo Aoki; Norihiko Kohyama; Yasushi Shinohara
Toxicology Letters | 2005
Hyung Jung Kim; Hae Yun Nam; Yamato Hiroshi; Yasushi Shinohara; Norihiko Kohyama; Hyoung Kyu Yun; Young Lim; Jung Sub Song