ArticleFood and chemical toxicology : an international journal published for the British Industrial Biological Research Association2017
Dose-response analysis of epigenetic, metabolic, and apical endpoints after short-term exposure to experimental hepatotoxicants.
Article in Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed.
- Epigenotoxicity: Decoding the epigenetic imprints of genotoxic agents and their implications for regulatory genetic toxicology.Environmental and molecular mutagenesis · 2025Review
- Anesthetic-induced epigenetic alterations: mechanisms and long-term clinical implications.Epigenetics · 2025Review
- Early microRNA responses in rodent liver mediated by furan exposure establish dose thresholds for later adverse outcomes.Toxicology letters · 2023Article
- Integration of Epigenetic Mechanisms into Non-Genotoxic Carcinogenicity Hazard Assessment: Focus on DNA Methylation and Histone Modifications.International journal of molecular sciences · 2021Review
- Loci specific epigenetic drug sensitivity.Nucleic acids research · 2020Article
- Early microRNA indicators of PPARα pathway activation in the liver.Toxicology reports · 2020Article
- Epigenetic Effects Mediated by Antiepileptic Drugs and their Potential Application.Current neuropharmacology · 2020Review
- Impact of obesity on the toxicity of a multi-ingredient dietary supplement, OxyELITE Pro™ (New Formula), using the novel NZO/HILtJ obese mouse model: Physiological and mechanistic assessments.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2018Article
- MicroRNAs as biomarkers for liver injury: Current knowledge, challenges and future prospects.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2017Review
- Safety assessment of the dietary supplement OxyELITE™ Pro (New Formula) in inbred and outbred mouse strains.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2017Article
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Authors and funding
14 authors.
Funding
Abstract
Identification of sensitive and novel biomarkers or endpoints associated with toxicity and carcinogenesis is of a high priority. There is increasing interest in the incorporation of epigenetic and metabolic biomarkers to complement apical data; however, a number of questions, including the tissue specificity, dose-response patterns, early detection of those endpoints, and the added value need to be addressed. In this study, we investigated the dose-response relationship between apical, epigenetic, and metabolomics endpoints following short-term exposure to experimental hepatotoxicants, clofibrate (CF) and phenobarbital (PB). Male F344 rats were exposed to PB (0, 5, 25, and 100 mg/kg/day) or CF (0, 10, 50, and 250 mg/kg/day) for seven days. Exposure to PB or CF resulted in dose-dependent increases in relative liver weights, hepatocellular hypertrophy and proliferation, and increases in Cyp2b1 and Cyp4a1 transcripts. These changes were associated with altered histone modifications within the regulatory units of cytochrome genes, LINE-1 DNA hypomethylation, and altered microRNA profiles. Metabolomics data indicated alterations in the metabolism of bile acids. This study provides the first comprehensive analysis of the apical, epigenetic and metabolic alterations, and suggests that the latter two occur within or near the dose response curve of apical endpoint alterations following exposure to experimental hepatotoxicants.
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