Cytotoxicity of environmentally relevant concentrations of aluminum in murine thymocytes and lymphocytes.

The effects of low concentrations of aluminum chloride on thymocytes and lymphocytes acutely dissociated from young mice were studied using flow cytometry with a DNA-binding dye. We demonstrate a rapid and dose-dependent injury in murine thymocytes and lymphocytes resulting from exposure to aluminum, as indicated by an increase in the entry into the cell of the DNA-binding dye, propidium iodine. A 60-minute exposure to 10 µM AlCl(3) caused damage of about 5% of thymocytes, while 50% were injured after 10 minutes at 20 µM. Nearly all thymocytes showed evidence of damage at 30 µM AlCl(3) after only 5 minutes of incubation. In lymphocytes, injury was observed at 15 µM AlCl(3) and less than 50% of cells were injured after a 60-minute exposure to 20 µM. Injury only rarely proceeded to rapid cell death and was associated with cell swelling. These results suggest that aluminum has cytotoxic effects on cells of the immune system.

Blood pressure and hypertension in relation to levels of serum polychlorinated biphenyls in residents of Anniston, Alabama.

OBJECTIVE: To determine risk factors for elevated blood pressure and hypertension in residents of Anniston, Alabama who live near a plant that manufactured polychlorinated biphenyls (PCBs). METHODS: A total of 758 Anniston residents had multiple measurements of blood pressure, provided information on demographic factors, medications, smoking, and exercise, and provided blood samples for determination of PCBs and total serum lipid. RESULTS: Rates of hypertension increased significantly (P < 0.05) with age and concentration of serum PCBs and were higher in African-Americans (n = 351) than in whites (n = 407). Hypertension also increased with BMI, but was not related to total serum lipid, sex, smoking, or exercise. Among 394 persons not on antihypertensive medication, linear regression analysis demonstrated a significant positive relation between serum PCB level and both systolic and diastolic blood pressure. After adjustment for potentially confounding variables, logistic regression gave odds ratios for the highest to lowest tertiles of total serum PCBs that exceeded 3.5 for both systolic and diastolic hypertension. When analyzed by quintiles of PCBs, the highest odds ratio was in the third quintile, suggesting a low dose effect. CONCLUSION: In individuals not on antihypertensive medication, serum PCB levels were significantly associated with prevalence of hypertension. Significant positive associations were also observed between PCB concentrations and systolic and diastolic blood pressure even in normotensive ranges. The strength of the relationships between PCB exposure and both hypertension and blood pressure suggests that PCB exposure may be an important contributing factor in regulation of blood pressure.

Cerebellar granule cell death induced by aluminum.

Using flow cytometry of acutely isolated cerebellar granule cell neurons, we have determined the effects of Al (III) on viability, membrane potential, intracellular calcium concentration and generation of reactive oxygen species (ROS). Al (III) killed granule cells in a time- and concentration-dependent fashion when monitored by use of the DNA-binding dye, propidium iodide. The threshold concentration was about 50 micromolar, and cell death at 100 micromolar was apparent after 30 min exposure and increased over time. Cell death was accompanied by cell swelling and a decrease in membrane potential, and was not dependent on external calcium concentration. While exposure to Al (III) was accompanied by an increase in ROS and an elevation of intracellular calcium concentration, calcium chelators and ROS scavengers did not reduce cell death. The action of Al (III) was not accompanied by activation of caspase-3 or an increase in annexin-V binding, both indicators of apoptosis. In the presence of intracellular O,O'-bis(2-aminophenyl)ethyleneglycol-N,N,N',N'-tetraacetic acid (BAPTA) and absence of extracellular calcium there was still a fluo-3 signal, which likely reflects an accumulation of intracellular Al (III). These observations suggest that the cell death is subsequent to intracellular accumulation of Al (III) and subsequent perturbation of cellular metabolism.