High-Throughput Screening Data Interpretation in the Context of In Vivo Transcriptomic Responses to Oral Cr(VI) Exposure Article Swipe
Julia E. Rager
,
Caroline Ring
,
Rebecca C. Fry
,
Mina Suh
,
Deborah M. Proctor
,
Laurie C. Haws
,
Mark Anglin Harris
,
Chad M. Thompson
·
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.17615/t33n-rd49
YOU?
·
· 2020
· Open Access
·
· DOI: https://doi.org/10.17615/t33n-rd49
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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- OA Status
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All OpenAlex metadata
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https://openalex.org/W4301222767Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.17615/t33n-rd49Digital Object Identifier
- Title
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High-Throughput Screening Data Interpretation in the Context of In Vivo Transcriptomic Responses to Oral Cr(VI) ExposureWork title
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articleOpenAlex work type
- Language
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enPrimary language
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2020Year of publication
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2020-04-22Full publication date if available
- Authors
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Julia E. Rager, Caroline Ring, Rebecca C. Fry, Mina Suh, Deborah M. Proctor, Laurie C. Haws, Mark Anglin Harris, Chad M. ThompsonList of authors in order
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https://doi.org/10.17615/t33n-rd49Publisher landing page
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
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https://doi.org/10.17615/t33n-rd49Direct OA link when available
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Context (archaeology), Transcriptome, Throughput, Interpretation (philosophy), In vivo, Computational biology, Biology, Computer science, Data mining, Genetics, Gene, Gene expression, Telecommunications, Wireless, Programming language, PaleontologyTop concepts (fields/topics) attached by OpenAlex
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| abstract_inverted_index.relevant | 60, 90, 187, 194 |
| abstract_inverted_index.tissues. | 77 |
| abstract_inverted_index.toxicity | 1 |
| abstract_inverted_index.(KCC#10). | 129 |
| abstract_inverted_index.Benchmark | 206 |
| abstract_inverted_index.Database. | 143 |
| abstract_inverted_index.anchoring | 211 |
| abstract_inverted_index.available | 14 |
| abstract_inverted_index.comparing | 64 |
| abstract_inverted_index.contrast, | 192 |
| abstract_inverted_index.duodenum, | 161 |
| abstract_inverted_index.endpoints | 89, 109 |
| abstract_inverted_index.including | 72 |
| abstract_inverted_index.responses | 146, 153, 216 |
| abstract_inverted_index.screening | 52 |
| abstract_inverted_index.sensitive | 157 |
| abstract_inverted_index.Evaluation | 78 |
| abstract_inverted_index.activation | 117 |
| abstract_inverted_index.consistent | 133 |
| abstract_inverted_index.contribute | 42, 237 |
| abstract_inverted_index.evaluating | 50 |
| abstract_inverted_index.hexavalent | 3 |
| abstract_inverted_index.identified | 85, 199 |
| abstract_inverted_index.intestinal | 249 |
| abstract_inverted_index.phenotypic | 210 |
| abstract_inverted_index.supporting | 243 |
| abstract_inverted_index.Carcinogens | 97 |
| abstract_inverted_index.Comparative | 141 |
| abstract_inverted_index.application | 26 |
| abstract_inverted_index.extensively, | 12 |
| abstract_inverted_index.genotoxicity | 120 |
| abstract_inverted_index.strengthened | 217 |
| abstract_inverted_index.non-mutagenic | 245 |
| abstract_inverted_index.proliferation | 227 |
| abstract_inverted_index.stress/injury | 224 |
| abstract_inverted_index.toxicological | 29 |
| abstract_inverted_index.understanding | 45 |
| abstract_inverted_index.Cr(VI)-induced | 248 |
| abstract_inverted_index.Toxicogenomics | 142 |
| abstract_inverted_index.investigators. | 105 |
| abstract_inverted_index.transcriptomic | 73, 152, 215 |
| abstract_inverted_index.Characteristics | 95 |
| abstract_inverted_index.high-throughput | 51 |
| abstract_inverted_index.death/proliferation | 128 |
| abstract_inverted_index.death/proliferation. | 190 |
| cited_by_percentile_year | |
| countries_distinct_count | 1 |
| institutions_distinct_count | 8 |
| citation_normalized_percentile.value | 0.30802523 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |