{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T01:50:14Z","timestamp":1744077014096,"version":"3.37.3"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T00:00:00Z","timestamp":1726444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Industrial Disease Clinical Research","award":["20316909"],"award-info":[{"award-number":["20316909"]}]},{"name":"Ministry of Health, Labor and Welfare"},{"name":"JSPS KAKENHI","award":["22K10512"],"award-info":[{"award-number":["22K10512"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Occupational exposure to 4,4\u2032-methylenebis(2-chloroaniline) (MOCA) has been linked to an increased risk of bladder cancer among employees in Japanese plants, indicating its significance as a risk factor for urinary bladder cancer. To investigate the role of MOCA metabolism in bladder carcinogenesis, we administered MOCA to non-humanized (F1-TKm30 mice) and humanized-liver mice for 4 and 28\u2009wk. We compared MOCA-induced changes in metabolic enzyme expression, metabolite formation, and effects on the urinary bladder epithelium in the 2 models. At week 4, MOCA exposure induced simple hyperplasia, cell proliferation, and DNA damage in the urothelium of the humanized-liver mice, whereas in the non-humanized mice, these effects were not observed. Notably, the concentration of 4-amino-4\u2032-hydroxylamino-3,3\u2032-dichlorodiphenylmethane (N-OH-MOCA) in the urine of humanized-liver mice was more than 10 times higher than that in non-humanized mice at the 4-wk mark. Additionally, we observed distinct differences in the expression of cytochrome P450 isoforms between the 2 models. Although no bladder tumors were detected after 28\u2009wk of treatment in either group, these findings suggest that N-OH-MOCA significantly contributes to the carcinogenic potential of MOCA in humans.<\/jats:p>","DOI":"10.1093\/toxsci\/kfae119","type":"journal-article","created":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T17:50:57Z","timestamp":1726595457000},"page":"210-219","source":"Crossref","is-referenced-by-count":1,"title":["Urinary bladder carcinogenic potential of 4,4\u2032-methylenebis(2-chloroaniline) in humanized-liver mice"],"prefix":"10.1093","volume":"202","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8938-9670","authenticated-orcid":false,"given":"Shugo","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Molecular Pathology, Osaka Metropolitan University Graduate School of Medicine , Osaka 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422-8526,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4233-4282","authenticated-orcid":false,"given":"Noriyuki","family":"Miyoshi","sequence":"additional","affiliation":[{"name":"Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka , Shizuoka 422-8526,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7696-5814","authenticated-orcid":false,"given":"Nao","family":"Yoneda","sequence":"additional","affiliation":[{"name":"Liver Engineering Laboratory, Department of Applied Research for Laboratory Animals, Central Institute for Experimental Medicine and Life Science (CIEM) , Kawasaki 210-0821,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shotaro","family":"Uehara","sequence":"additional","affiliation":[{"name":"Liver Engineering Laboratory, Department of Applied Research for Laboratory Animals, Central Institute for Experimental Medicine and Life Science (CIEM) , Kawasaki 210-0821,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuka","family":"Yokota","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Osaka Metropolitan University Graduate School of Medicine , Osaka 545-8585,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ikue","family":"Noura","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Osaka Metropolitan University Graduate School of Medicine , Osaka 545-8585,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaki","family":"Fujioka","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Osaka Metropolitan University Graduate School of Medicine , Osaka 545-8585,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arpamas","family":"Vachiraarunwong","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Osaka Metropolitan University Graduate School of Medicine , Osaka 545-8585,","place":["Japan"]},{"name":"Department of Environmental Risk Assessment, Osaka Metropolitan University Graduate School of Medicine , Osaka 545-8585,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Kakehashi","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Osaka Metropolitan University Graduate School of Medicine , Osaka 545-8585,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3706-2454","authenticated-orcid":false,"given":"Hiroshi","family":"Suemizu","sequence":"additional","affiliation":[{"name":"Liver Engineering Laboratory, Department of Applied 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