LITHIUM INHIBITS GROWTH IN A MURINE NEURAL PRECURSOR CELL LINE

The influence of lithium on cell growth and cell viability was studied in short-term cultures of a neural precursor cell line (NT) developed from a murine teratocarcinoma. At very low concentrations ranging from 0.1 m to 1 m Li₂CO₃(equivalent to therapeutic blood concentrations) there was no difference between untreated and treated cultures. 10 m lithium (Li⁺) was found to be toxic with 33% of cell death, while there was inhibition of growth without cell death at concentrations of 2.5 m and 5 m of Li⁺. In experiments where 2.5 m Li⁺was added at the time of seeding, there was growth arrest on day 1 followed by recovery on day 2. Flow cytometric analysis revealed that cells treated with Li⁺were blocked in S phase. At 5 m concentration of Li⁺, the recovery occurred on day 3 and the plating efficiency was significantly low. The ability to form colonies in soft agar was reduced at 2.5 m and 5 m concentrations of Li⁺to an equal extent. Thus, Li⁺has growth inhibitory as well as anchorage-independent growth reducing effects. The NT cell line therefore would be a good model system to study the mechanism of teratogenic effect of Li⁺.