ABSTRACT
In this chapter, the authors summarize the data that led to this hypothesis, describe our more recent studies of the membrane-associated inhibitors of DNA synthesis in senescent and quiescent Human diploid fibroblasts, and describe experiments that test the genetic predictions of this hypothesis. In contrast, carcinogen-transformed Human Diploid Fibroblasts (HDF) are not able to induce DNA synthesis in senescent HDF nuclei; rather, the transformed nuclei in these heterodikaryons are inhibited from entering S phase. The quiescent HDF membrane-associated inhibitor shows the same sensitivity to heat, trypsin, and periodate as the senescent HDF inhibitor. Therefore, these data are in keeping with the possibility that senescent and quiescent HDF have the same inhibitor. In addition, the kinetics of DNA synthesis inhibition or induction are the same in heterodikaryons formed between a given type of replicative cell (e.g., HDF or HeLa) and either senescent or quiescent HDF.
