ArticleToxicological sciences : an official journal of the Society of Toxicology2011
Investigation of the mode of action underlying the tumorigenic response induced in B6C3F1 mice exposed orally to hexavalent chromium.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 92 citations in OpenAlex.
- Heavy metals: toxicity and human health effects.Archives of toxicology · 2025Review
- Mechanism of Mitochondrial Kinetic Imbalance and Nrf2 Signaling Pathway-Mediated Oxidative Stress in Nickel and/or Chromium-Induced Kidney Injury in Mice.Antioxidants (Basel, Switzerland) · 2024Article
- Article
- The Toxicological Risk Assessment (TRA) of Total Chromium Impurities in Menthae piperitae tinctura (Mentha x piperita L., folium) Available in Polish Pharmacies Including Regulatory Approaches with Special Emphasis of Cr Speciation and Genotoxicity.Biological trace element research · 2023Article
- Coenzyme Q10, Biochanin A and Phloretin Attenuate Cr(VI)-Induced Oxidative Stress and DNA Damage by Stimulating Nrf2/HO-1 Pathway in the Experimental Model.Biological trace element research · 2023Article
- 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
- Article
- 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
- Hexavalent chromium promotes differential binding of CTCF to its cognate sites in Euchromatin.Epigenetics · 2021Article
- Assessment of Mechanistic Data for Hexavalent Chromium-Induced Rodent Intestinal Cancer Using the Key Characteristics of Carcinogens.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Toxic Mechanisms of Five Heavy Metals: Mercury, Lead, Chromium, Cadmium, and Arsenic.Frontiers in pharmacology · 2021Review
- Metals and molecular carcinogenesis.Carcinogenesis · 2020Review
- 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
- Mechanisms of Chromium-Induced Toxicity.Current opinion in toxicology · 2019Article
- Mutant Frequency is not Increased in Mice Orally Exposed to Sodium Dichromate.Food safety (Tokyo, Japan) · 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
- Comparison of Toxicity and Recovery in the Duodenum of B6C3F1 Mice Following Treatment with Intestinal Carcinogens Captan, Folpet, and Hexavalent Chromium.Toxicologic pathology · 2017Article
- High-Throughput Screening Data Interpretation in the Context of In Vivo Transcriptomic Responses to Oral Cr(VI) Exposure.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
- Transcriptomic responses in the oral cavity of F344 rats and B6C3F1 mice following exposure to Cr(VI): Implications for risk assessment.Environmental and molecular mutagenesis · 2016Article
- Reevaluation and Classification of Duodenal Lesions in B6C3F1 Mice and F344 Rats from 4 Studies of Hexavalent Chromium in Drinking Water.Toxicologic pathology · 2016Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic ingestion of high concentrations of hexavalent chromium [Cr(VI)] in drinking water induces intestinal tumors in mice. To investigate the mode of action (MOA) underlying these tumors, a 90-day drinking water study was conducted using similar exposure conditions as in a previous cancer bioassay, as well as lower (heretofore unexamined) drinking water concentrations. Tissue samples were collected in mice exposed for 7 or 90 days and subjected to histopathological, biochemical, toxicogenomic, and toxicokinetic analyses. Described herein are the results of toxicokinetic, biochemical, and pathological findings. Following 90 days of exposure to 0.3-520 mg/l of sodium dichromate dihydrate (SDD), total chromium concentrations in the duodenum were significantly elevated at ≥ 14 mg/l. At these concentrations, significant decreases in the reduced-to-oxidized glutathione ratio (GSH/GSSG) were observed. Beginning at 60 mg/l, intestinal lesions were observed including villous cytoplasmic vacuolization. Atrophy, apoptosis, and crypt hyperplasia were evident at ≥ 170 mg/l. Protein carbonyls were elevated at concentrations ≥ 4 mg/l SDD, whereas oxidative DNA damage, as assessed by 8-hydroxydeoxyguanosine, was not increased in any treatment group. Significant decreases in the GSH/GSSG ratio and similar histopathological lesions as observed in the duodenum were also observed in the jejunum following 90 days of exposure. Cytokine levels (e.g., interleukin-1β) were generally depressed or unaltered at the termination of the study. Overall, the data suggest that Cr(VI) in drinking water can induce oxidative stress, villous cytotoxicity, and crypt hyperplasia in the mouse intestine and may underlie the MOA of intestinal carcinogenesis in mice.
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