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 embryonal cells. [3H]Thymidine incorporation of non-committed mouse P19 embryonal carcinoma cells was inhibited by lithium treatment. Similar effects were seen in a variety of other cells. This growth inhibition occurred in the G2 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 indicate that lithium might disturb embryonal development through interference in embryonal cell cycle regulation.
Smits
V A
VA
Department of Hematology, University Medical Center Utrecht G03.647, The Netherlands.
Essers
M A
MA
Loomans
D S
DS
Klompmaker
R
R
Rijksen
G
G
Medema
R H
RH
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D019926:Cyclin B / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000187:drug effects; D008094:Lithium / Q000494:pharmacology*; D051379:Mice; D015739:Nocodazole / Q000494:pharmacology; D013997:Time Factors
D019926:Cyclin B; D006131:Growth Inhibitors; D006657:Histones; D008094:Lithium; D016203:CDC2 Protein Kinase; D015739:Nocodazole