X-rays induce dose-dependent and cell cycle-independent accumulation of p21(sdi1/WAF1).
Cell cycle arrest at the G1 checkpoint is governed by a function of wild-type p53. 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 p21(sdi1/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 p21(sdi1/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 p21(sdi1/WAF1). Furthermore, an accumulation of p53 and p21(sdi1/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 p21(sdi1/WAF1) accumulation mechanism exists throughout the cell cycle, and that the signal strength induced by X-irradiation is dose-dependent.
Tsuyama
N
N
Department of Radiobiology, Radiation Effects Research Foundation, Hiroshima, Japan.
Ide
T
T
Noda
A
A
Iwamoto
K S
KS
Mizuno
T
T
Kyoizumi
S
S
Seyama
T
T
D002453:Cell Cycle; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D016193:G1 Phase; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D007700:Kinetics; D012333:RNA, Messenger / Q000378:metabolism; D011829:Radiation Dosage; D016192:Resting Phase, Cell Cycle; D016196:S Phase; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014965:X-Rays
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53