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Because the administration of 2\u2010acetylaminofluorene (2AAF) followed by a partial hepatectomy, selectively induces the HPC proliferation, we investigated the effects of chronic 2AAF administration on the HCC development caused by the chronic administration of the carcinogen diethylnitrosamine (DEN) for 16 weeks in the rat. DEN\u2009+\u20092AAF protocol impeded weight gain of animals but promoted prominent hepatomegaly and exacerbated liver alterations compared to DEN protocol alone. The tumor areas detected by \u03b3\u2010glutamyl transferase, prostaglandin reductase\u20101, and glutathione S\u2010transferase <jats:italic>Pi<\/jats:italic>\u22121 liver cancer markers increased up to 80% as early as 12 weeks of treatment, meaning 6 weeks earlier than DEN alone. This protocol also increased the number of Ki67\u2010positive cells and those of CD90 and CK19, two well\u2010known progenitor cell markers. Interestingly, microarray analysis revealed that DEN\u2009+\u20092AAF protocol differentially modified the global gene expression signature and induced the differential expression of 30 genes identified as HPC markers as early as 6 weeks of treatment. In conclusion, 2AAF induces the early appearance of HPC markers and as a result, accelerates the hepatocarcinogenesis induced by DEN in the rat. Thus, since 2AAF simultaneously administrated with DEN enriches HPC during hepatocarcinogenesis, we propose that DEN\u2009+\u20092AAF protocol might be a useful tool to investigate the cellular origin of HCC with progenitor features.<\/jats:p>","DOI":"10.1002\/mc.23298","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T20:26:42Z","timestamp":1616704002000},"page":"377-390","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Enrichment of progenitor cells by 2\u2010acetylaminofluorene accelerates liver carcinogenesis induced by diethylnitrosamine in vivo"],"prefix":"10.1002","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8670-1219","authenticated-orcid":false,"given":"Mar\u00eda Paulette","family":"Castro\u2010Gil","sequence":"first","affiliation":[{"name":"Laboratory of Liver Diseases National Institute of Genomic Medicine  Ciudad de M\u00e9xico 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