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.

Sex-Dependent Effects of Cadmium Exposure in Early Life on Gut Microbiota and Fat Accumulation in Mice

“…Previous toxicity studies of cadmium have focused on kidney and bone damage, and epidemiologic evidences have linked low-level cadmium exposure with adverse effects including diabetes, hypertension, peripheral artery disease, and cancers ( Adams et al 2014 ; Edwards and Ackerman 2016 ; Eum et al 2008 ; Julin et al 2012 ; Navas-Acien et al 2005 ; Romano et al 2015 ). However, in functional studies based on animal models, the dosage of cadmium was much higher than the mean intake of populations ( Du et al 2015 ; L Liu et al 2015 ; Y Liu et al 2014 ). In this work, we used 100 nM cadmium in drinking water, which is equivalent ~ 2.5 μg/kg BW per week and closely corresponds to the TWI and the mean intake by humans.…”

Baicalein ameliorates cadmium-induced hepatic and renal oxidative damage in rats

“…Cadmium possesses cytotoxic, carcinogenic, and mutagenic properties (Du et al, 2015). It causes hepatotoxicity and nephrotoxicity by acute administration (Ezedom and Asagba, 2016).…”

The Dysbiosis of Gut Microbiota Caused by Low-Dose Cadmium Aggravate the Injury of Mice Liver through Increasing Intestinal Permeability

“…Previous studies have demonstrated that Cd is toxic to the kidney and bones, and low-dose Cd exposure is also associated with some adverse effects such as cancers, diabetes, hypertension and some other chronic diseases [1,8,10]. However, the Cd dosages used in most studies are higher than the human intake through drinking water or diets [24,25]. It is not suitable to evaluate the Cd toxicity under the environmental low dose.…”