Cytotoxicity and mitotic alterations induced by non-genotoxic lithium salts in CHO cells in vitro

Aneugenic compounds are able to cause chromosome missegregation during mitosis which results in aneuploidy in cells that are able to survive. Aneuploidy is considered a key early condition in the progression from a normal cell into a cancerous cell. The possible toxicity of therapeutic lithium has raised concern because lithium salts are currently widely prescribed as an efficient treatment of manic-depressive disorders and numerous undesirable side effects of long-term treatment have been reported to date. We have observed a dose-dependent cytotoxic effect of both Li2CO3 and LiCl in AA8 CHO cells, while no genotoxic damage was detected. Mitotic abnormalities such as multipolar anaphases and lagging chromosomes leading to the presence of micronuclei in the next interphase were frequently observed after treatment with lithium salts. Thus, the effectiveness of both lithium salts to induce alterations in the normal segregation of chromosomes could be ascribed to interference with proteins involved in the organization and/or function of the mitotic apparatus.