X-rays Induce Dose-dependent and Cell Cycle-independent Accumulation of p21sdi1/WAF1

Cell cycle arrest at the G1 checkpoint is governed by a function ofwild-typep53. We assessed the behavior of the sdi1 gene, which codes for a 21kDa potent inhibitor of cdk/cyclins, after X-irradiation. X-irradiation induced sdi1 mRNA accumulation and G1 arrest only in cells possessing wild-type p53. Elevation of p21sdi1/WAF1 was preceded by p53 accumulation, which occurred despite p53 mRNA constancy in normal cells growing in the log phase. The quantity of accumulated p53 and p21sdi1/WAF1 was radiation dose dependent. A decrease in the S phase cell population in normal cells observed after irradiation reached a minimum at less-than-maximum levels of p53 and p21sdi1/WAF1 Furthermore, an accumulation of p53 and p21sdi1/WAF1 was also observed when cells were synchronized in the G0, G1 and S phase and X-irradiated. These results indicated that an X-ray induced p53 and p21sdi1/WAF1 accumulation mechanism exists throughout the cell cycle, and that the signal strength induced by X-irradiation is dose-dependent.