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However, whether maternal cadmium exposure accelerates liver cancer in the offspring is unknown. This study investigated the impact of early\u2010life exposure to cadmium on the incidence and potential mechanisms of hepatocellular carcinoma (HCC) in offspring subjected to postweaning HCC induction. HCC in C57BL\/6J mice was induced by diethylnitrosamine (DEN) injection at weaning, followed by a long\u2010term high\u2010fat choline\u2010deficient (HFCD) diet. Before weaning, liver cadmium levels were significantly higher in mice with early\u2010life cadmium exposure than in those without cadmium exposure. However, by 26 and 29 weeks of age, hepatic cadmium fell to control levels, while a significant decrease was observed in copper and iron in the liver. Both male and female cadmium\u2010exposed mice showed increased body weight compared to non\u2010cadmium\u2010treated mice. For females, early\u2010life cadmium exposure also worsened insulin intolerance but did not significantly promote DEN\/HFCD diet\u2010induced liver tumors. In contrast, in male mice, early\u2010life cadmium exposure enhanced liver cancer induction by DEN\/HFCD with high incidence and larger liver tumors. The liver peritumor tissue of early\u2010life cadmium\u2010exposed mice exhibited greater inflammation and disruption of fatty acid metabolism, accompanied by higher malondialdehyde and lower esterified triglyceride levels compared to mice without cadmium exposure. These findings suggest that early\u2010life exposure to low\u2010dose cadmium accelerates liver cancer development induced by a DEN\/HFCD in male mice, probably due to chronic lipotoxicity and inflammation caused by increased uptake but decreased consumption of fatty acids.<\/jats:p>","DOI":"10.1155\/2021\/1427787","type":"journal-article","created":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T02:08:48Z","timestamp":1638151728000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Early\u2010Life Exposure to Low\u2010Dose Cadmium Accelerates Diethylnitrosamine and Diet\u2010Induced Liver Cancer"],"prefix":"10.1155","volume":"2021","author":[{"given":"Hongbo","family":"Men","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie 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