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In the current study, we sought to clarify the involvement of CAs in chemical carcinogenesis using a rat model with a pure CA\u2010inducer hepatocarcinogen, acetamide. Whole\u2010genome analysis indicated that hepatic tumors induced by acetamide treatment for 26\u201330\u2009weeks showed a broad range of copy number alterations in various chromosomes. In contrast, hepatic tumors induced by a typical mutagen (diethylnitrosamine) followed by a nonmutagen (phenobarbital) did not show such mutational patterns. Additionally, structural alterations such as translocations were observed more frequently in the acetamide\u2010induced tumors. Moreover, most of the acetamide\u2010induced tumors expressed c\u2010Myc and\/or MDM2 protein due to the copy number gain of each oncogene. These results suggest the occurrence of chromosomal rearrangements and subsequent oncogene amplification in the acetamide\u2010induced tumors. Taken together, the results indicate that CAs are directly involved in tumorigenesis through chromosomal rearrangements in an acetamide\u2010induced hepatocarcinogenesis rat model.<\/jats:p>","DOI":"10.1111\/cas.16324","type":"journal-article","created":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T00:18:56Z","timestamp":1725841136000},"page":"3612-3621","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Chromosome aberrations cause tumorigenesis through chromosomal rearrangements in a hepatocarcinogenesis rat model"],"prefix":"10.1111","volume":"115","author":[{"given":"Kenji","family":"Nakamura","sequence":"first","affiliation":[{"name":"Division of Pathology National Institute of Health Sciences  Kawasaki Japan"},{"name":"Laboratory of Veterinary Pathology Tokyo University of Agriculture and Technology  Tokyo 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