Sequence of cell life phases in a finitely proliferative population of cultured rat cells: a genealogical study.

Family trees of rat liver epitheliallike cells (RLECs), which proliferate finitely in primary culture, were obtained by time-lapse cinemicrography (TLC). In family trees, RLECs were classified into those terminated with division (class D cells), those terminated with incomplete division (class l cells), i.e., division followed by fusion of two daughter cells, and the combined population (class N cells) of those terminated with death and those surviving for 120 hr or more with their termination not detected by TLC. The interphase period, but not the intersibling period, of class D cells became distributed more broadly with time on the family tree. These results for class D cells fit best to a transition probability model with two indeterminate states (Brooks et al., Cell, 19:493-504, 1980) when the model is modified in such a way that the transition probability for one of the two indeterminate states decreases with time. During proliferation of RLECs, some of the class D cells reproduce, while others showed transition, in part by way of class l cells, to class N cells. The frequency of transition from class D to class N increased with time in the family tree. Two sibling cells of a parent mitotic cell were simultaneously either class D or class N at a significantly high frequency, suggesting that the transition had been determined in the preceding cells. The present observations confirm previously described observations on human diploid cells, and in addition, reveal some new details of the finitely proliferative nature of somatic diploid cells.