Synchrotron-Based Imaging of Chromium and γ-H2AX Immunostaining in the Duodenum Following Repeated Exposure to Cr(VI) in Drinking Water
| Autor: | Christopher R. Kirman, Liz Mittal, Rock J. Vitale, Ryan Tappero, Sean Hays, Mina Suh, Jeffrey C. Wolf, Laurie C. Haws, Deborah M. Proctor, Jennifer M. Seiter, Chad M. Thompson, Mark Harris, Mark A. Chappell |
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| Rok vydání: | 2014 |
| Předmět: |
Chromium
Pathology medicine.medical_specialty Time Factors Cr(VI) Duodenum Crypt Toxicology Risk Assessment digestive system Synchrotron Imaging of Chromium in the Gut Intestinal absorption Histones Mice chemistry.chemical_compound mode of action Intestinal mucosa Duodenal Neoplasms synchrotron Chromates medicine Animals H2AX Intestinal Mucosa Hexavalent chromium Carcinogen hexavalent chromium Hyperplasia Microvilli digestive oral and skin physiology Spectrometry X-Ray Emission medicine.disease Immunohistochemistry Molecular biology Rats Inbred F344 Cell Transformation Neoplastic medicine.anatomical_structure Intestinal Absorption chemistry Microspectrophotometry Female carcinogenesis Synchrotrons Water Pollutants Chemical Immunostaining DNA Damage |
| Zdroj: | Toxicological Sciences |
| ISSN: | 1096-0929 1096-6080 |
| DOI: | 10.1093/toxsci/kfu206 |
| Popis: | Current drinking water standards for chromium are for the combined total of both hexavalent and trivalent chromium (Cr(VI) and Cr(III)). However, recent studies have shown that Cr(III) is not carcinogenic to rodents, whereas mice chronically exposed to high levels of Cr(VI) developed duodenal tumors. These findings may suggest the need for environmental standards specific for Cr(VI). Whether the intestinal tumors arose through a mutagenic or non-mutagenic mode of action (MOA) greatly impacts how drinking water standards for Cr(VI) are derived. Herein, X-ray fluorescence (spectro)microscopy (m-XRF) was used to image the Cr content in the villus and crypt regions of duodena from B6C3F1 mice exposed to 180 mg/l Cr(VI) in drinking water for 13 weeks. DNA damage was also assessed by c-H2AX immunostaining. Exposure to Cr(VI) induced villus blunting and crypt hyperplasia in the duodenum—the latter evidenced by lengthening of the crypt compartment by � 2-fold with a concomitant 1.5-fold increase in the number of crypt enterocytes. c-H2AX immunostaining was elevated in villi, but not in the crypt compartment. m-XRF maps revealed mean Cr levels >30 times higher in duodenal villi than crypt regions; mean Cr levels in crypt regions were only slightly above background signal. Despite the presence of Cr and elevated c-H2AX immunoreactivity in villi, no aberrant foci indicative of transformation were evident. These findings do not support a MOA for intestinal carcinogenesis involving direct Cr-DNA interaction in intestinal stem cells, but rather support a non-mutagenic MOA involving chronic wounding of intestinal villi and crypt cell hyperplasia. |
| Databáze: | OpenAIRE |
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