title: Cadmium-induced microsatellite instability in the kidneys and leukocytes of C57BL/6J mice.
abstract: 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.
authors.affiliation: Department of Laboratory Animal Science, School of Basic Medical Science, Capital Medical University, Beijing, 100069, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Du
authors.affiliation: Laboratory Animal Center, Jilin University, Changchun, Jilin, 130062, China.
authors.forename: Tianfeng
authors.initials: T
authors.lastname: Lan
authors.affiliation: Department of Laboratory Animal Science, School of Basic Medical Science, Capital Medical University, Beijing, 100069, China.
authors.forename: Bao
authors.initials: B
authors.lastname: Yuan
authors.affiliation: Department of Laboratory Animal Science, School of Basic Medical Science, Capital Medical University, Beijing, 100069, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Laboratory Animal Science, School of Basic Medical Science, Capital Medical University, Beijing, 100069, China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Laboratory Animal Science, School of Basic Medical Science, Capital Medical University, Beijing, 100069, China.
authors.forename: Wenzhi
authors.initials: W
authors.lastname: Ren
authors.affiliation: Laboratory Animal Center, Jilin University, Changchun, Jilin, 130062, China.
authors.forename: Zhenwen
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002104:Cadmium / Q000633:toxicity*; D019256:Cadmium Chloride / Q000633:toxicity; D007668:Kidney / Q000187:drug effects*; D007962:Leukocytes / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053842:Microsatellite Instability / Q000187:drug effects*; D018895:Microsatellite Repeats / Q000187:drug effects; D009153:Mutagens / Q000633:toxicity; D009154:Mutation / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000473:pathology
chemical_list: D009153:Mutagens; D002104:Cadmium; D019256:Cadmium Chloride
keywords: C57BL/6J mice; cadmium chloride; microsatellite instability