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 mM to 1 mM Li2CO3 (equivalent to therapeutic blood concentrations) there was no difference between untreated and treated cultures. 10 mM 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 mM and 5 mM of Li+. In experiments where 2.5 mM 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 mM 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 mM and 5 mM 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+.