Inhibition of cell proliferation by lithium is associated with interference in cdc2 activation

Lithium can interfere with embryonal development in a variety of organisms. We investigated the effect of lithium on the proliferation of early embryo nal cells. [H-3]Thymidine incorporation of non-committed mouse P19 embryona l carcinoma cells was inhibited by lithium treatment. Similar effects were seen in a variety of other cells. This growth inhibition occurred in the G( 2) phase, since cells accumulated with a 4N DNA content, but the appearance of mitotic cells was blocked. Lithium could also prevent the activation of cdc2, thereby inhibiting cyclin B/cdc2 kinase activity. These data indicat e that lithium might disturb embryonal development through interference in embryonal cell cycle regulation. (C) 1999 Federation of European Biochemica l Societies.