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Toxicol Appl Pharmacol
| Title: | Western diet unmasks transient low-level vinyl chloride-induced tumorigenesis; potential role of the (epi-)transcriptome |
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| Author(s): | Liu S; He L; Bannister OB; Li J; Schnegelberger RD; Vanderpuye CM; Althouse AD; Schopfer FJ; Wahlang B; Cave MC; Monga SP; Zhang X; Arteel GE; Beier JI; |
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| Address: | "Department of Pathology, University of Pittsburgh, United States of America; Pittsburgh Liver Research Center, Pittsburgh, PA 15213, United States of America. Electronic address: Shl96@pitt.edu. Department of Chemistry, University of Louisville, Louisville, KY 40208, United States of America. Electronic address: liqing.he@louisville.edu. Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition University of Pittsburgh, United States of America. Electronic address: obb4@pitt.edu. Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition University of Pittsburgh, United States of America. Electronic address: jil35@pitt.edu. Department of Pharmacology and Chemical Biology, University of Pittsburgh, United States of America. Electronic address: regdel32@gmail.com. Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition University of Pittsburgh, United States of America. Electronic address: cmv59@pitt.edu. Division of General Internal Medicine, University of Pittsburgh, Pittsburgh, PA 15213, United States of America. Electronic address: ada62@pitt.edu. Pittsburgh Liver Research Center, Pittsburgh, PA 15213, United States of America; Department of Pharmacology and Chemical Biology, University of Pittsburgh, United States of America. Electronic address: fjschopfer@katz.pitt.edu. Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40202, United States of America; Superfund Research Center, University of Louisville, Louisville, KY 40202, United States of America; Hepatobiology and Toxicology Center, University of Louisville, Louisville, KY 40202, United States of America; Center for Integrative Environmental Health Sciences, University of Louisville, Louisville, KY 40202, United States of America; University of Louisville Alcohol Research Center, Louisville, KY 40202, United States of America. Electronic address: banrida.wahlang@louisville.edu. Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville School of Medicine, Louisville, KY 40202, United States of America; Superfund Research Center, University of Louisville, Louisville, KY 40202, United States of America; Hepatobiology and Toxicology Center, University of Louisville, Louisville, KY 40202, United States of America; Center for Integrative Environmental Health Sciences, University of Louisville, Louisville, KY 40202, United States of America; University of Louisville Alcohol Research Center, Louisville, KY 40202, United States of America; Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, United States of America; Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY 40202, United States of America; Liver Transplant Program at UofL Health-Jewish Hospital Trager Transplant Center, Louisville, KY 40202, United States of America; The Robley Rex Veterans Affairs Medical Center, Louisville, KY 40206, United States of America. Electronic address: matt.cave@louisville.edu. Department of Pathology, University of Pittsburgh, United States of America; Pittsburgh Liver Research Center, Pittsburgh, PA 15213, United States of America; Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition University of Pittsburgh, United States of America. Electronic address: smonga@pitt.edu. Department of Chemistry, University of Louisville, Louisville, KY 40208, United States of America; Hepatobiology and Toxicology Center, University of Louisville, Louisville, KY 40202, United States of America; Center for Integrative Environmental Health Sciences, University of Louisville, Louisville, KY 40202, United States of America; University of Louisville Alcohol Research Center, Louisville, KY 40202, United States of America. Electronic address: xiang.zhang@louisville.edu. Pittsburgh Liver Research Center, Pittsburgh, PA 15213, United States of America; Department of Environmental and Occupational Health University of Pittsburgh, Pittsburgh, PA 15213, United States of America. Electronic address: gearteel@pitt.edu. Pittsburgh Liver Research Center, Pittsburgh, PA 15213, United States of America; Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition University of Pittsburgh, United States of America; Department of Environmental and Occupational Health University of Pittsburgh, Pittsburgh, PA 15213, United States of America. Electronic address: jibeier@pitt.edu" |
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| Journal Title: | Toxicol Appl Pharmacol |
| Year: | 2023 |
| Volume: | 20230414 |
| Issue: | |
| Page Number: | 116514 - |
| DOI: | 10.1016/j.taap.2023.116514 |
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| ISSN/ISBN: | 1096-0333 (Electronic) 0041-008X (Print) 0041-008X (Linking) |
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| 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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| Keywords: | "Mice Animals *Vinyl Chloride/toxicity/metabolism Transcriptome *Carcinoma, Hepatocellular/pathology Diet, Western *Liver Neoplasms/chemically induced/genetics/metabolism Liver/metabolism *Non-alcoholic Fatty Liver Disease/metabolism Carcinogenesis/metabol;" |
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| Notes: | "MedlineLiu, Silvia He, Liqing Bannister, Olivia B Li, Jiang Schnegelberger, Regina D Vanderpuye, Charis-Marie Althouse, Andrew D Schopfer, Francisco J Wahlang, Banrida Cave, Matthew C Monga, Satdarshan P Zhang, Xiang Arteel, Gavin E Beier, Juliane I eng K01 DK096042/DK/NIDDK NIH HHS/ P50 AA024337/AA/NIAAA NIH HHS/ R35 ES028373/ES/NIEHS NIH HHS/ S10 OD020106/OD/NIH HHS/ R21 ES031531/ES/NIEHS NIH HHS/ P42 ES023716/ES/NIEHS NIH HHS/ R01 DK133454/DK/NIDDK NIH HHS/ R21 ES031510/ES/NIEHS NIH HHS/ R01 ES032189/ES/NIEHS NIH HHS/ P20 GM113226/GM/NIGMS NIH HHS/ P30 DK120531/DK/NIDDK NIH HHS/ P30 ES030283/ES/NIEHS NIH HHS/ R03 DK107912/DK/NIDDK NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2023/04/16 Toxicol Appl Pharmacol. 2023 Jun 1; 468:116514. doi: 10.1016/j.taap.2023.116514. Epub 2023 Apr 14" |
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