Comparison of the Effects of Hexavalent Chromium in the Alimentary Canal of F344 Rats and B6C3F1 Mice Following Exposure in Drinking Water: Implications for Carcinogenic Modes of Action
| Autor: | Charles D. Hébert, J. Gregory Hixon, Deborah M. Proctor, Howard G. Shertzer, Chad M. Thompson, Mina Suh, Mark A. Harris, Jill F. Mann, Laurie C. Haws |
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| Rok vydání: | 2011 |
| Předmět: |
Chromium
Male medicine.medical_specialty Pathology Cr(VI) Carcinogenicity Tests Iron Administration Oral Mice Inbred Strains Biology Toxicology medicine.disease_cause Jejunum Mice chemistry.chemical_compound MOA Species Specificity Intestinal mucosa Internal medicine medicine oxidative stress Animals Intestinal Mucosa Hexavalent chromium Gastrointestinal Neoplasms Dose-Response Relationship Drug Drinking Water Mouth Mucosa Glutathione Environmental Toxicology Rats Inbred F344 Rats Dose–response relationship Endocrinology medicine.anatomical_structure chemistry Sodium dichromate Duodenum Cytokines Female Lipid Peroxidation carcinogenesis Oxidative stress |
| Zdroj: | Toxicological Sciences |
| ISSN: | 1096-0929 1096-6080 |
| DOI: | 10.1093/toxsci/kfr280 |
| Popis: | Exposure to high concentrations of hexavalent chromium (Cr[VI]) in drinking water is reported to induce oral mucosa tumors in F344 rats and intestinal tumors in B6C3F1 mice. To investigate the modes of action underlying these tumors, 90-day drinking water studies (with interim necropsy at day 8) were conducted with concentrations of 0.1-182 mg/l Cr(VI), administered as 0.3-520 mg/l sodium dichromate dihydrate. Blood and tissue samples were analyzed for chromium content, oxidative stress, iron levels, and gross and microscopic lesions. Results for the F344 rats are described herein and compared with results from B6C3F1 mice published previously. After 90 days of exposure, total chromium concentrations in the rat and mouse oral mucosae were comparable, yet significant dose-dependent decreases in the reduced-to-oxidized glutathione ratio (GSH/GSSG) were observed only in rats. In the duodenum, changes in GSH/GSSG were only observed in mice. Levels of 8-hydroxydeoxyguanosine were not increased in the oral or duodenal mucosae of either species. Glutathione levels were increased in the duodenum but decreased in the jejunum of both species, indicating potential differential responses in the intestinal segments. Histiocytic infiltration was observed in the duodenum of both species, yet duodenal cytokines were repressed in mice but increased in rats. Serum and bone marrow iron levels were more decreased in rats than mice. Collectively, these data suggest that Cr(VI)-induced carcinogenesis in the rodent alimentary canal involves oxidative stress; however, differences in histopathology, cytokines, and iron status suggest potential contributions from other factors as well. |
| Databáze: | OpenAIRE |
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