Immortalization in Culture of Rat Cells: A Genealogic Study

The process of immortalization of cultured rat liver epithelial-like cells from JAR-2 rats was studied by time-lapse cinemicrography. This process was shown to be multistep. First (in the F-phase), cells were similar to those in a finitely proliferative population. Most cells terminated their proliferative life in the F-phase, while a few gained additional proliferative potential and subsequently entered into the T (transitional)-phase. In the T-phase, a population of cells maintained proliferative potential with a large fluctuation: Some cells further gained additional proliferative potential while others lost it. After a period in the T-phase, continuously dividing cells emerged (in the I-phase). The interphase period of the dividing cells in both the T- and the F-phases showed cells to distribute exponentially, consistent with transitional probability models. However, cells in the l-phase were distributed much more narrowly and were frequently close to a normal distribution. Hypothetical mechanisms of immortalization were presented on the basis of these observations.