Cellular targets of lead neurotoxicity: in vitro models

Four types of cells in culture were exposed to lead (Pb) acetate (0.1-1000 microM): astroglia-enriched, oligodendroglia-enriched, and meningeal fibroblast cultures prepared from neonatal rat brains; and human neuroblastoma cultures prepared from the SK-N-SH-SY5Y cell line. The viability (trypan blue dye exclusion and proliferation) of these cell types after Pb exposure was compared in order to identify cellular targets in the central nervous system that were directly susceptible to cytotoxicity. Of the 4 cell types tested, only oligodendroglia showed marked sensitivity to Pb treatment. However, proliferation of the SY5Y cells was temporarily inhibited if the cells were treated 1 day (but not 3 days) after seeding. The potential for thiamin, which is used to treat Pb intoxication in cattle, to prevent this effect was tested. Rather than preventing this toxic effect, however, thiamin (1 mM) exacerbated that inhibition of proliferation. Astroglia and meningeal fibroblasts, which were resistant to Pb toxicity, were shown by atomic absorption analysis to take up Pb from the culture medium and concentrate it intracellularly to at least 55X the extracellular concentration, thus supporting hypotheses that these cells act as Pb sinks in the brain.