Cadmium increases ferroportin-1 gene expression in J774 macrophage cells via the production of reactive oxygen species

Cadmium intoxication has been associated with the dysregulation of iron homeostasis. In the present study, we investigated the effect of cadmium on the expression of ferroportin 1 (FPN1), an important iron transporter protein that is involved in iron release from macrophages. When we incubated cadmium with J774 mouse macrophage cells, FPN1 mRNA levels were significantly increased in a dose- and time-dependent manner. Furthermore, the cadmium-induced FPN1 mRNA expression was associated with increased levels of FPN1 protein. On the other hand, cadmium-mediated FPN1 mRNA induction in J774 cells was completely blocked when cells were co-treated with a transcription inhibitor, acitomycin D. Also, cadmium directly stimulated the activity of the FPN1-promoter driven luciferase reporter, suggesting that the cadmium up-regulates FPN1 gene expression in a transcription-dependent manner. Finally, cadmium exposure to J774 macrophages increased intracellular reactive oxygen species (ROS) levels by ~ 2-fold, compared to untreated controls. When J774 cells were co-treated with antioxidant N-acetylcystein, the cadmium-induced FPN1 mRNA induction was significantly attenuated. In summary, the results of this study clearly demonstrated that cadmium increased FPN1 expression in macrophages through a mechanism that involves ROS production, and suggests another important interaction between iron and cadmium metabolism

Evaluation of the Webler-Brown model for estimating tetrachloroethylene exposure from vinyl-lined asbestos-cement pipes

<p>Abstract</p> <p>Background</p> <p>From May 1968 through March 1980, vinyl-lined asbestos-cement (VL/AC) water distribution pipes were installed in New England to avoid taste and odor problems associated with asbestos-cement pipes. The vinyl resin was applied to the inner pipe surface in a solution of tetrachloroethylene (perchloroethylene, PCE). Substantial amounts of PCE remained in the liner and subsequently leached into public drinking water supplies.</p> <p>Methods</p> <p>Once aware of the leaching problem and prior to remediation (April-November 1980), Massachusetts regulators collected drinking water samples from VL/AC pipes to determine the extent and severity of the PCE contamination. This study compares newly obtained historical records of PCE concentrations in water samples (n = 88) with concentrations estimated using an exposure model employed in epidemiologic studies on the cancer risk associated with PCE-contaminated drinking water. The exposure model was developed by Webler and Brown to estimate the mass of PCE delivered to subjects' residences.</p> <p>Results</p> <p>The mean and median measured PCE concentrations in the water samples were 66 and 0.5 μg/L, respectively, and the range extended from non-detectable to 2432 μg/L. The model-generated concentration estimates and water sample concentrations were moderately correlated (Spearman rank correlation coefficient = 0.48, p < 0.0001). Correlations were higher in samples taken at taps and spigots vs. hydrants (ρ = 0.84 vs. 0.34), in areas with simple vs. complex geometry (ρ = 0.51 vs. 0.38), and near pipes installed in 1973–1976 vs. other years (ρ = 0.56 vs. 0.42 for 1968–1972 and 0.37 for 1977–1980). Overall, 24% of the variance in measured PCE concentrations was explained by the model-generated concentration estimates (p < 0.0001). Almost half of the water samples had undetectable concentrations of PCE. Undetectable levels were more common in areas with the earliest installed VL/AC pipes, at the beginning and middle of VL/AC pipes, at hydrants, and in complex pipe configurations.</p> <p>Conclusion</p> <p>PCE concentration estimates generated using the Webler-Brown model were moderately correlated with measured water concentrations. The present analysis suggests that the exposure assessment process used in prior epidemiological studies could be improved with more accurate characterization of water flow. This study illustrates one method of validating an exposure model in an epidemiological study when historical measurements are not available.</p