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Lead levels in the breast milk of nursing Andean mothers living in a lead-contaminated environmentConcentrations of lead (Pb) in breast milk (PbM) and blood (PbB) were measured in a current cohort of lactating mothers living in Andean communities where women of childbearing age engage in the occupational use of Pb, and compared to results obtained in earlier studies. Mean PbM concentration in the current group of breastfeeding mothers tested in 2012/2013 was 3.73 mug/L (SD: 7.3; range: 0.049-28.04), and significantly lower than the 9.83 mug/L (SD: 12.75; range: 0.2-49) previously observed in breastfeeding mothers in the study area from 1999 to 2007. Breastfeeding women in the current cohort showed an average PbM/PbB ratio of 3.6%, which is in agreement with other studies. The mean PbB level obtained for the current cohort was 7.8 mug/dl (SD: 5.2; range: 1.4-21), and significantly lower than the mean PbB level of 20.8 mug/dl (SD: 16.4; range: 4-73) obtained for the comparison group of breastfeeding mothers tested between 1999 and 2007. A correlation of .687 between paired PbM and maternal PbB was found, indicating that maternal PbB level is a significant predictor of PbM. Current PbM levels remain higher than international averages, but indicate that maternal Pb exposure has declined over time in the environmentally Pb-contaminated study area. The current reduction in Pb in milk and blood of breastfeeding mothers may be due to adherence to a Pb-exposure education and prevention program initiated by the authors in the study area years earlier, as well as recent improvements in local health care delivery.
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Generation and characterization of hammerhead ribozymes targeting rodent metallothionein-I and -II ribonucleic acidTwo trans-acting hammerhead ribozymes (Rzs), Rz1-2 and Rz4-9, were designed and shown to be effective in cleaving rat or mouse metallothenein (MT)-I and MT-II mRNA, respectively, at position +147/148, in a sequence-specific manner. The catalytic efficiency for Rz1-2 on rat MT-I was found to be 678 M(-1)s(-1) and that for Rz4-9 on rat MT-II cRNA was found to be 372 M(-1)s(-1). An expression vector, pRz(4-9/1-2), containing both Rzs linked in tandem, was constructed and used to transfect NbE-1 cells, an immortalized ventral prostate epithelial cell line. Two stable-transfected lines, NbE-1(Rz2) and NbE-1(Rz3), expressing substantial levels of (Rz1-2/Rz4-9) and minimal levels of MT-I and MT-II transcripts were found to exhibit increased sensitivity to cadmium (Cd)-induced cytotoxicity compared to the parent line. This article is the first to report successful degradation of rodent MT mRNA in vitro and in cellulo by hammerhead Rzs.
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Evidence that erythroid-type glucose transporter intrinsic activity is modulated by cadmium treatment of mouse 3T3-L1 cellsPrevious studies suggest that regulation of hexose uptake in Chinese hamster ovary fibroblasts can occur by alterations in glucose transporter intrinsic activity without changes in cell surface transporter number (Harrison, S. A., Buxton, J. M., Helgerson, A. L., MacDonald, R. G., Chlapowski, F. J., Carruthers, A., and Czech, M. P. (1990) J. Biol. Chem. 265, 5793-5801). We tested this hypothesis using 3T3-L1 fibroblasts and adipocytes which exhibit 5-6-fold increases in 2-deoxyglucose or 3-O-methylglucose uptake when exposed to low micromolar concentrations of cadmium for 18 h. Cadmium treatment decreased the apparent Km of 3T3-L1 fibroblasts for 3-O-methylglucose influx from approximately 28 to 9 mM and increased the apparent Vmax by 2-3-fold. These fibroblasts lack the skeletal muscle/adipocyte-type (GLUT4) transporter and showed only a small increase in total cellular immunoreactive HepG2 type (GLUT1) transporter in response to cadmium. Furthermore, cell surface GLUT1 levels did not change in 3T3-L1 fibroblasts exposed to cadmium, as assessed by the binding to intact cells of an antibody which recognizes an extracellular GLUT1 epitope. Insulin enhanced 2-deoxyglucose uptake 2-fold in 3T3-L1 fibroblasts, but did not further stimulate cadmium-activated transport rates. In contrast, insulin stimulated hexose transport 15-fold in 3T3-L1 adipocytes, which express both GLUT1 and GLUT4 proteins, and this effect was fully additive with the 5-fold effect of cadmium. Cadmium had little or no effect on immunoreactive GLUT1 or GLUT4 in isolated 3T3-L1 adipocyte plasma membranes. In contrast, insulin action led to marked recruitment (3-fold) of GLUT4 to the plasma membrane fraction in adipocytes treated with or without cadmium. Taken together, these data are consistent with the hypothesis that cadmium-activated sugar uptake is catalyzed by GLUT1, whereas insulin-stimulated sugar uptake is catalyzed predominantly by GLUT4 in 3T3-L1 adipocytes. Furthermore, the data suggest that the GLUT1 transporter can undergo significant increases in intrinsic catalytic activity in response to cadmium treatment of 3T3-L1 fibroblasts and adipocytes.