“…Upon induction of p21, Tet-p21-1 and other Tet-p21 cells became larger, suggesting that they continued to grow in the absence of DNA replication, a phenomenon that is also observed in ®broblast senescence (Cristofalo et al, 1989). Consistent with this, a tenfold increase of p21 RNA has been observed as human ®broblasts become senescent (Noda et al, 1994), and increases in p21 RNA and protein are also found when human ®broblasts immortalized by the temperature-sensitive simian virus 40 T antigen are shifted to nonpermissive temperature, resulting in morphological characteristics of senescent ®broblasts (Tsao et al, 1995 other p53-dependent genes are also induced in irradiated cells, it is likely that p21 is responsible for cell cycle arrest. Consistent with this idea, it has been reported that the induced level of p21 in U.V.-irradiated cells is su cient to account for the observed inhibition Cdk2 activity, and may in part account for the decrease in Cdk4 activity (Poon et al, 1996).…”