ArticleToxicological sciences : an official journal of the Society of Toxicology2017
High-Throughput Screening Data Interpretation in the Context of In Vivo Transcriptomic Responses to Oral Cr(VI) Exposure.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Decoding Short- and Long-Term Cellular Adaptations to Cr(VI) Exposure Through High-Throughput Transcriptomics.International journal of medical sciences · 2026Article
- A workflow for human health hazard evaluation using transcriptomic data and Key Characteristics-based gene sets.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- The placenta epigenome-brain axis: placental epigenomic and transcriptomic responses that preprogram cognitive impairment.Epigenomics · 2022Article
- Article
- Crypt and Villus Transcriptomic Responses in Mouse Small Intestine Following Oral Exposure to Hexavalent Chromium.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- Inferred inactivation of the Cftr gene in the duodena of mice exposed to hexavalent chromium (Cr(VI)) in drinking water supports its tumor-suppressor status and implies its potential role in Cr(VI)-induced carcinogenesis of the small intestines.Toxicology and applied pharmacology · 2021Article
- Development of the genomic inflammatory index (GII) to assess key maternal antecedents associated with placental inflammation.Placenta · 2021Article
- Predictive modeling of biological responses in the rat liver usingComputational toxicology (Amsterdam, Netherlands) · 2021Article
- Identifying the Transcriptional Response of Cancer and Inflammation-Related Genes in Lung Cells in Relation to Ambient Air Chemical Mixtures in Houston, Texas.Environmental science & technology · 2020Article
- A role for microRNAs in the epigenetic control of sexually dimorphic gene expression in the human placenta.Epigenomics · 2020Article
- Comparison of Gene Expression Responses in the Small Intestine of Mice Following Exposure to 3 Carcinogens Using the S1500+ Gene Set Informs a Potential Common Adverse Outcome Pathway.Toxicologic pathology · 2019Article
- The use of evidence from high-throughput screening and transcriptomic data in human health risk assessments.Toxicology and applied pharmacology · 2019Article
- Identifying Attributes That Influence In Vitro-to-In Vivo Concordance by Comparing In Vitro Tox21 Bioactivity Versus In Vivo DrugMatrix Transcriptomic Responses Across 130 Chemicals.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Integration of mechanistic and pharmacokinetic information to derive oral reference dose and margin-of-exposure values for hexavalent chromium.Journal of applied toxicology : JAT · 2018Article
- Benchmark Dose Modeling Estimates of the Concentrations of Inorganic Arsenic That Induce Changes to the Neonatal Transcriptome, Proteome, and Epigenome in a Pregnancy Cohort.Chemical research in toxicology · 2017Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The toxicity of hexavalent chromium [Cr(VI)] in drinking water has been studied extensively, and available in vivo and in vitro studies provide a robust dataset for application of advanced toxicological tools to inform the mode of action (MOA). This study aimed to contribute to the understanding of Cr(VI) MOA by evaluating high-throughput screening (HTS) data and other in vitro data relevant to Cr(VI), and comparing these findings to robust in vivo data, including transcriptomic profiles in target tissues. Evaluation of Tox21 HTS data for Cr(VI) identified 11 active assay endpoints relevant to the Ten Key Characteristics of Carcinogens (TKCCs) that have been proposed by other investigators. Four of these endpoints were related to TP53 (tumor protein 53) activation mapping to genotoxicity (KCC#2), and four were related to cell death/proliferation (KCC#10). HTS results were consistent with other in vitro data from the Comparative Toxicogenomics Database. In vitro responses were compared to in vivo transcriptomic responses in the most sensitive target tissue, the duodenum, of mice exposed to ≤ 180 ppm Cr(VI) for 7 and 90 days. Pathways that were altered both in vitro and in vivo included those relevant to cell death/proliferation. In contrast, pathways relevant to p53/DNA damage were identified in vitro but not in vivo. Benchmark dose modeling and phenotypic anchoring of in vivo transcriptomic responses strengthened the finding that Cr(VI) causes cell stress/injury followed by proliferation in the mouse duodenum at high doses. These findings contribute to the body of evidence supporting a non-mutagenic MOA for Cr(VI)-induced intestinal cancer.
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