In vitro toxicity of methyl mercury: effects on nerve growth factor (NGF)-responsive neurons and on NGF synthesis in fibroblasts.

The effect of methyl mercury chloride (MeHgCl) on the chick sympathetic and sensory dorsal root ganglia was studied in a biological in vitro assay. These cultures were not affected by the addition of MeHg up to a concentration of 2 microM. However, after an addition of 4-5 microM MeHg the capability of the neurons to respond to added nerve growth factor (NGF) was completely inhibited. The effect of MeHg was also examined in a fibroblast cell line, mouse 3T3 cells. After the addition of mercury to the culture medium at concentrations as low as 0.1 microM, an elevated production of the NGF protein was observed. However, NGF mRNA measured in the individual fibroblast cells by in situ hybridization was found to be reduced to about 80% of the control in the low level at day 2 of exposure. These results suggest that the release of NGF is actively enhanced from the 3T3 cells by addition of low levels of mercury. The results thus show that MeHg at low to moderate concentrations has adverse effects on NGF responses in cultured neurons and moreover alter levels of NGF production in cells, suggestive of mechanisms for mercury toxicity in the developing nervous system.