Gene expression and epigenetic alterations in human hepatocytes treated with low doses of chemical carcinogens
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ABSTRACT: The increasing number of man-made chemicals in the environment that may pose a carcinogenic risk emphasizes the need for the development of reliable time- and cost-effective approaches for carcinogen detection. To address this issue, we have investigated the utility of human hepatocytes for the in vitro identification of genotoxic and non-genotoxic carcinogens. Induced pluripotent stem cell (iPSC)-derived human hepatocytes were treated with the genotoxic carcinogens aflatoxin B1 (AFB1) and benzo[a]pyrene (B[a]P) and with the non-genotoxic liver carcinogen methapyrilene at non-cytotoxic concentrations for 7 days, and transcriptomic profile was examined. 1569 (892 protein-coding and 677 non-coding), 1693 (922 protein-coding and 771 non-coding), and 2061 (1462 protein-coding and 599 non-coding) differentially expressed genes were detected in cells treated with AFB1, B[a]P, and methapyrilene, respectively. Additionally, we examined the toxicogenomics response to AFB1, B[a]P, and methapyrilene exposure in human HepaRG cells and demonstrated that carcinogens had a less prominent effect on the cellular transcriptome as compared to that in human iPSC-derived hepatocytes. Overall, the results demonstrate that the prime non-genotoxic effect of exposure to carcinogens, regardless of their mode of action, in short-term in vitro testing is a profound global transcriptome response, indicating a greater value of toxicogenomics for rapid carcinogen screening in vitro.
ORGANISM(S): Homo sapiens
PROVIDER: GSE127791 | GEO | 2019/03/05
REPOSITORIES: GEO
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