These authors contributed equally to this work.
Cadmium-induced microsatellite instability in the kidneys and leukocytes of C57BL/6J mice
Version of Record online: 5 JAN 2014
© 2014 Wiley Periodicals, Inc.
Volume 30, Issue 6, pages 683–692, May/June 2015
How to Cite
Du, X., Lan, T., Yuan, B., Chen, J., Hu, J., Ren, W. and Chen, Z. (2015), Cadmium-induced microsatellite instability in the kidneys and leukocytes of C57BL/6J mice. Environ. Toxicol., 30: 683–692. doi: 10.1002/tox.21946
- Issue online: 17 MAY 2015
- Version of Record online: 5 JAN 2014
- Manuscript Accepted: 21 DEC 2013
- Manuscript Revised: 15 DEC 2013
- Manuscript Received: 5 SEP 2013
- National Science Foundation of China . Grant Number: 30970420, 31172168, and 31071988
- cadmium chloride;
- microsatellite instability;
- C57BL/6J mice
Cadmium is a cytotoxic, carcinogenic, and mutagenic industrial product or byproduct. The correlation between metal exposure and microsatellite instability (MSI) has been reported by several groups. In the present study, 50 C57BL/6J mice at 6 weeks of age were divided into five groups and intraperitoneally injected with 0, 0.25, 0.5, 1, or 2 mg/kg cadmium chloride quaque die alterna for 4 weeks. Then, the liver, kidney, testis, leukocytes, bone marrow, and small intestine were collected from the treated mice and weighed. Portions of these tissues were fixed for further histological analysis, and the remaining tissues were subjected to genomic DNA extraction for the analysis of a panel of 42 microsatellite markers. The liver and testis weight coefficients were significantly changed in the 1 and 2 mg/kg cadmium chloride-treated groups compared with the control group. Simultaneously, severe histopathologic changes in the liver and kidneys, along with a complete disorganization of testicular structure and obvious severe necrosis in the testes were observed in the cadmium-treated group. The cadmium accumulated in the liver and kidneys of the mice in all cadmium-treated groups; the tissue cadmium concentrations were significantly higher than those in the control group. After STR scanning, MSI was found at three loci (D15Mit5, D10Mit266, and DxMit172) in the kidneys and leukocytes of mice in the lower dose groups (0.25 and 0.5 mg/kg). In summary, we have successfully established a sub-chronic cadmium exposure model and confirmed that cadmium exposure can induce MSI in mice. We also identified two loci that could be regarded as “hotspots” of microsatellite mutation in mice. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 683–692, 2015.