Glucocorticoid potentiation of lead neurotoxicity in the mouse HN9 hippocampal cell line.
The biochemical events underlying neurobehavioural deficits following persistent low-level lead exposure during embryonic and early postnatal development remain unclear. Because glucocorticoids have previously been demonstrated to potentiate the action of certain neurotoxins, their role in low-level lead-mediated neurotoxicity was examined using a glucocorticoid-responsive immortalized hippocampal neural cell line (HN9). Low-level lead (10(-10)m) reduced the cell number by approximately 30% over a 5-day treatment period. This effect was potentiated by treatment with the synthetic glucocorticoid dexamethasone, with a 52% decrease in cell number. Lead toxicity in actively differentiating cells was also potentiated by dexamethasone. However, while neither lead nor dexamethasone alone was toxic for cells that had previously been induced to differentiate, a combination of both drugs significantly reduced cell number. These results suggest that lead is preferentially toxic in actively dividing cells and that glucocorticoids may play a role in the potentiation of the lead-induced neurotoxicity.
Hayes
F D
FD
Department of Pharmacology and Clinical Pharmacology, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, UK.
Breen
K C
KC