Culture condition-dependent senescence-like growth arrest and immortalization in rodent embryo cells

We investigated the telomerase activity, telomere length, and replicative l ife span of cells from human embryos and rodent embryos (mouse, rat and Syr ian hamster). We used two culture conditions for rodent embryo cells whereb y the cells were plated at a density of 2 x 10(5) into a 25-cm(2) flask and subcultured every 3 days or every 10 days. We found that nearly 100% of th e cultures of rodent embryo cells become immortal when they are subcultured using the 10-day culture protocol, These rodent embryo cells retain telome rase activity and long telomeres (19-50 kb) in the long-term cultures, wher eas human embryo cells rapidly deplete telomerase activity associated with significant shortening of telomeres, and then they senesce. In contrast to the results from 10-day cultures, we found that some mouse cell cultures an d most Syrian hamster cell cultures arrest cell growth after 13 and 29 popu lation doublings, respectively, while retaining substantial levels of telom erase activity and experiencing no significant loss of telomeres when the c ells were subcultured using the 3-day culture protocol. This growth arrest is phenotypically indistinguishable from cellular senescence. The present r esults suggest that in rodent cells the onset of senescence-like arrest can be activated without repression of telomerase, and that this activation pa thway can be bypassed easily under certain culture conditions, such as the 10-day culture protocol. (C) 2001 by Radiation Research Society.