Article ; Online: Western diet unmasks transient low-level vinyl chloride-induced tumorigenesis; potential role of the (epi-)transcriptome.
Toxicology and applied pharmacology
2023 Volume 468, Page(s) 116514
Abstract: Background & aims: Vinyl chloride (VC) monomer is a volatile organic compound commonly used in industry. At high exposure levels, VC causes liver cancer and toxicant-associated steatohepatitis. However, lower exposure levels (i.e., sub-regulatory ... ...
| Abstract | Background & aims: Vinyl chloride (VC) monomer is a volatile organic compound commonly used in industry. At high exposure levels, VC causes liver cancer and toxicant-associated steatohepatitis. However, lower exposure levels (i.e., sub-regulatory exposure limits) that do not directly damage the liver, enhance injury caused by Western diet (WD). It is still unknown if the long-term impact of transient low-concentration VC enhances the risk of liver cancer development. This is especially a concern given that fatty liver disease is in and of itself a risk factor for the development of liver cancer. Methods: C57Bl/6 J mice were fed WD or control diet (CD) for 1 year. During the first 12 weeks of feeding only, mice were also exposed to VC via inhalation at sub-regulatory limit concentrations (<1 ppm) or air for 6 h/day, 5 days/week. Results: Feeding WD for 1 year caused significant hepatic injury, which was exacerbated by VC. Additionally, VC increased the number of tumors which ranged from moderately to poorly differentiated hepatocellular carcinoma (HCC). Transcriptomic analysis demonstrated VC-induced changes in metabolic but also ribosomal processes. Epitranscriptomic analysis showed a VC-induced shift of the modification pattern that has been associated with metabolic disease, mitochondrial dysfunction, and cancer. Conclusions: These data indicate that VC sensitizes the liver to other stressors (e.g., WD), resulting in enhanced tumorigenesis. These data raise concerns about potential interactions between VC exposure and WD. It also emphasizes that current safety restrictions may be insufficient to account for other factors that can influence hepatotoxicity. |
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| MeSH term(s) | Mice ; Animals ; Vinyl Chloride/toxicity ; Vinyl Chloride/metabolism ; Transcriptome ; Carcinoma, Hepatocellular/pathology ; Diet, Western ; Liver Neoplasms/chemically induced ; Liver Neoplasms/genetics ; Liver Neoplasms/metabolism ; Liver/metabolism ; Non-alcoholic Fatty Liver Disease/metabolism ; Carcinogenesis/metabolism ; Cell Transformation, Neoplastic/metabolism | |||||
| Chemical Substances | Vinyl Chloride (WD06X94M2D) | |||||
| Language | English | |||||
| Publishing date | 2023-04-14 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 204477-8 | |||||
| ISSN | 1096-0333 ; 0041-008X | |||||
| ISSN (online) | 1096-0333 | |||||
| ISSN | 0041-008X | |||||
| DOI | 10.1016/j.taap.2023.116514 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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