The influence of cellular proliferative history on the susceptibility to oncogenic transformation

C3H mouse 10T1/2 clone 8 cells were serially transferred from passage 11 to 15 with 5 x 10(4) cells seeded per 60-mm dish at each passage. One group of cells was passaged as soon as confluence was reached. Two other groups were kept for 3 or 6 days in confluence at each passage before subculture. Cloning efficiency was found to increase progressively with passage of all three groups. At the 15th passage, cells from all three groups were harvested just prior to confluence, irradiated with ultraviolet light, and assayed for clonogenic survival and malignant transformation. Survival response was the same for all three groups, but cells which were kept constantly proliferating in previous passages were found to be much more susceptible to transformation. These results suggest that the susceptibility of these cells to transformation is influenced by their proliferative history; in particular, intermittent growth quiescence in previous passages decreased this susceptibility.