{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:36:36Z","timestamp":1790094996891,"version":"4.0.1"},"reference-count":36,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,26]],"date-time":"2023-12-26T00:00:00Z","timestamp":1703548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health, Labor and Welfare, Japan","award":["20316909"],"award-info":[{"award-number":["20316909"]}]},{"name":"Ministry of Health, Labor and Welfare, Japan","award":["20KD1002"],"award-info":[{"award-number":["20KD1002"]}]},{"name":"Ministry of Health, Labor and Welfare, Japan","award":["22K10512"],"award-info":[{"award-number":["22K10512"]}]},{"name":"Ministry of Health, Labor and Welfare, Japan","award":["20ck0106545h0001"],"award-info":[{"award-number":["20ck0106545h0001"]}]},{"name":"Ministry of Health, Labor and Welfare, Japan","award":["CH24027"],"award-info":[{"award-number":["CH24027"]}]},{"name":"JSPS KAKENHI","award":["20316909"],"award-info":[{"award-number":["20316909"]}]},{"name":"JSPS KAKENHI","award":["20KD1002"],"award-info":[{"award-number":["20KD1002"]}]},{"name":"JSPS KAKENHI","award":["22K10512"],"award-info":[{"award-number":["22K10512"]}]},{"name":"JSPS KAKENHI","award":["20ck0106545h0001"],"award-info":[{"award-number":["20ck0106545h0001"]}]},{"name":"JSPS KAKENHI","award":["CH24027"],"award-info":[{"award-number":["CH24027"]}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["20316909"],"award-info":[{"award-number":["20316909"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["20KD1002"],"award-info":[{"award-number":["20KD1002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["22K10512"],"award-info":[{"award-number":["22K10512"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["20ck0106545h0001"],"award-info":[{"award-number":["20ck0106545h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["CH24027"],"award-info":[{"award-number":["CH24027"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shimadzu Corporation","award":["20316909"],"award-info":[{"award-number":["20316909"]}]},{"name":"Shimadzu Corporation","award":["20KD1002"],"award-info":[{"award-number":["20KD1002"]}]},{"name":"Shimadzu Corporation","award":["22K10512"],"award-info":[{"award-number":["22K10512"]}]},{"name":"Shimadzu Corporation","award":["20ck0106545h0001"],"award-info":[{"award-number":["20ck0106545h0001"]}]},{"name":"Shimadzu Corporation","award":["CH24027"],"award-info":[{"award-number":["CH24027"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Occupational exposure to aromatic amines (AAs) is an important risk factor for urinary bladder cancer. This study aimed to evaluate the toxicity of AAs and analyze the carcinogenic mechanisms in rat bladder by comprehensive analysis of DNA adducts (DNA adductome). DNA was extracted from the bladder epithelia of rats treated with AAs, including acetoacet-o-toluidine (AAOT) and o-toluidine (OTD), and adductome analysis was performed. Principal component analysis\u2013discriminant analysis revealed that OTD and AAOT observed in urinary bladder hyperplasia could be clearly separated from the controls and other AAs. After confirming the intensity of each adduct, four adducts were screened as having characteristics of the OTD\/AAOT treatment. Comparing with the in-house DNA adduct database, three of four candidates were identified as oxidative DNA adducts, including 8-OH-dG, based on mass fragmentation together with high-resolution accurate mass (HRAM) spectrometry data. Therefore, findings suggested that oxidative stress may be involved in the toxicity of rat bladder epithelium exposed to AAs. Consequently, the administration of apocynin, an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase, in six-week-old rats fed with 0.6% OTD in their diet resulted in simple hyperplastic lesions in the bladder that were suppressed by apocynin. The labeling indices of Ki67, \u03b3-H2AX, and 8-OHdG were significantly decreased in an apocynin concentration-dependent manner. These findings indicate that oxidative stress may have contributed to the development of urinary cancer induced by OTD.<\/jats:p>","DOI":"10.3390\/biom14010036","type":"journal-article","created":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T02:58:12Z","timestamp":1703645892000},"page":"36","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Evaluation of the Mechanisms Involved in the Development of Bladder Toxicity following Exposure to Occupational Bladder Cancer Causative Chemicals Using DNA Adductome Analysis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8938-9670","authenticated-orcid":false,"given":"Shugo","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Molecular Pathology, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Gi","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan"},{"name":"Department of Environmental Risk Assessment, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masami","family":"Komiya","sequence":"additional","affiliation":[{"name":"Laboratory of Environmental Toxicology and Carcinogenesis, School of Pharmacy, Nihon University, Chiba 274-8555, Japan"},{"name":"Division of Cancer Pathophysiology, National Cancer Center Research Institute, Tokyo 104-0045, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asuka","family":"Obikane","sequence":"additional","affiliation":[{"name":"Division of Cancer Pathophysiology, National Cancer Center Research Institute, Tokyo 104-0045, Japan"},{"name":"Department of Biochemistry, University of Yamanashi, Shimokato 1110, Chuo 409-3898, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arpamas","family":"Vachiraarunwong","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan"},{"name":"Department of Environmental Risk Assessment, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0048-2874","authenticated-orcid":false,"given":"Masaki","family":"Fujioka","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1149-1450","authenticated-orcid":false,"given":"Anna","family":"Kakehashi","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukari","family":"Totsuka","sequence":"additional","affiliation":[{"name":"Laboratory of Environmental Toxicology and Carcinogenesis, School of Pharmacy, Nihon University, Chiba 274-8555, Japan"},{"name":"Division of Cancer Pathophysiology, National Cancer Center Research Institute, Tokyo 104-0045, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Wanibuchi","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3322\/caac.21763","article-title":"Cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J. 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