{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:32:11Z","timestamp":1760146331380,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T00:00:00Z","timestamp":1729123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Center Research and Development Fund","award":["23-A-8","25-A-5","26-A-8","18ck0106264h0002","20ck0106545h0001"],"award-info":[{"award-number":["23-A-8","25-A-5","26-A-8","18ck0106264h0002","20ck0106545h0001"]}]},{"name":"Japan Agency for Medical Research and Development","award":["23-A-8","25-A-5","26-A-8","18ck0106264h0002","20ck0106545h0001"],"award-info":[{"award-number":["23-A-8","25-A-5","26-A-8","18ck0106264h0002","20ck0106545h0001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Determining a novel etiology and mechanism of human cancer requires extraction of characteristic mutational signatures derived from chemical substances. This study explored the mutational signatures of N-nitroso bile acid conjugates using Salmonella strains. Exposing S. typhimurium TA1535 to N-nitroso-glycine\/taurine bile acid conjugates induced a predominance of C:G to T:A transitions. Two mutational signatures, B1 and B2, were extracted. Signature B1 is associated with N-nitroso-glycine bile acid conjugates, while Signature B2 is linked to N-nitroso-taurine bile acid conjugates. Signature B1 revealed a strong transcribed strand bias with GCC and GCT contexts, and the mutation pattern of N-nitroso-glycine bile acid conjugates in YG7108, which lacks O6-methylguanine DNA methyltransferases, matched that of the wild-type strain TA1535, suggesting that O6-methyl-deoxyguanosine contributes to mutations in the relevant regions. COSMIC database-based similarity analysis revealed that Signature B1 closely resembled SBS42, which is associated with occupational cholangiocarcinoma caused by overexposure to 1,2-dichlolopropane (1,2-DCP) and\/or dichloromethane (DCM). Moreover, the inflammatory response pathway was induced by 1,2-DCP exposure in a human cholangiocyte cell line, and iNOS expression was positive in occupational cholangiocarcinomas. These results suggest that 1,2-DCP triggers an inflammatory response in biliary epithelial cells by upregulating iNOS and N-nitroso-glycine bile acid conjugate production, resulting in cholangiocarcinoma via DNA adduct formation.<\/jats:p>","DOI":"10.3390\/ijms252011191","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T05:03:49Z","timestamp":1729227829000},"page":"11191","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Whole Genome Sequencing Analysis of Model Organisms Elucidates the Association Between Environmental Factors and Human Cancer Development"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2731-8097","authenticated-orcid":false,"given":"Shinya","family":"Hasegawa","sequence":"first","affiliation":[{"name":"Department of Environmental Health Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7837-3411","authenticated-orcid":false,"given":"Yutaka","family":"Shoji","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, Shizuoka Eiwa Gakuin University Junior College, 1769 Ikeda, Suruga-ku, Shizuoka 422-8545, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mamoru","family":"Kato","sequence":"additional","affiliation":[{"name":"Division of Bioinformatics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asmaa","family":"Elzawahry","sequence":"additional","affiliation":[{"name":"Division of Bioinformatics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Momoko","family":"Nagai","sequence":"additional","affiliation":[{"name":"Division of Bioinformatics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1642-8127","authenticated-orcid":false,"given":"Min","family":"Gi","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8938-9670","authenticated-orcid":false,"given":"Shugo","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideki","family":"Wanibuchi","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sachiyo","family":"Mimaki","sequence":"additional","affiliation":[{"name":"Division of Translational Informatics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7507-2349","authenticated-orcid":false,"given":"Katsuya","family":"Tsuchihara","sequence":"additional","affiliation":[{"name":"Division of Translational Informatics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukari","family":"Totsuka","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1016\/j.csbj.2024.01.024","article-title":"A review on trends in development and translation of omics signatures in cancer","volume":"23","author":"Ma","year":"2024","journal-title":"Comput. 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