Modulation of mammalian cell growth by a choline analog, N-isopropylethanolamine.
The choline analog, N-isopropylethanolamine (IPE), inhibits the growth of both Chinese hamster ovary CHO-K1 and mouse L-M cells by two kinetically distinct mechanisms; I, a reversible and concentration-dependent reduction in the logarithmic population doubling rate and the saturation density of cultures by low IPE levels in the media; and II, an irreversible and time-dependent killing of cells by high IPE concentrations. Both types of inhibition are independent of media depletion, cell density, or the time of treatment after cell plating; however, the actual IPE concentration that is necessary to elicit Type I or Type II inhibition in each cell line is dependent on the choline level of the media. Ethanolamine, methionine, or betaine have no effect on IPE-induced growth inhibition. From a mutagenized population of CHO-K1 cells we isolated variant cell strains that are resistant to the lethal effect of IPE. It was determined that with both the wild type and variant strains the sensitivity of cells to growth inhibition by IPE (both Type I and Type II) was proportional to the degree by which choline uptake was inhibited by the analog. Retinoic acid, which inhibits the growth of some fibroblast and epithelial cell lines by a concentration-dependent reduction in population doubling rate and saturation density, behaves synergistically with IPE to inhibit the growth of CHO-K1 cells. Dibutyryl cyclic AMP, on the other hand, causes only an additive increase in the growth inhibition of CHO-K1 populations that also are treated with IPE.
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D003470:Culture Media; D004261:DNA Replication / Q000187:drug effects; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D007739:L Cells / Q000187:drug effects / Q000502:physiology; D051379:Mice; D010053:Ovary; D011437:Propylamines / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology
D003470:Culture Media; D004983:Ethanolamines; D011437:Propylamines; C008203:2-isopropylaminoethanol; D014212:Tretinoin