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X-rays induce dose-dependent and cell cycle-independent accumulation of p21(sdi1/WAF1)

N Tsuyama1, T Ide, A Noda

  • 1Department of Radiobiology, Radiation Effects Research Foundation, Hiroshima, Japan.

Hiroshima Journal of Medical Sciences
|April 21, 2001
PubMed

Insights

Wild-type p53 triggers cell cycle arrest at the G1 checkpoint. X-irradiation dose-dependently increases p53 and p21(sdi1/WAF1) accumulation, inhibiting cell division.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Radiation Biology

Background:

  • Wild-type p53 protein is a critical regulator of the G1 cell cycle checkpoint.
  • The sdi1 gene encodes p21(sdi1/WAF1), a potent inhibitor of cyclin-dependent kinases (cdks) and cyclins.

Purpose of the Study:

  • To investigate the behavior of the sdi1 gene and its encoded protein, p21(sdi1/WAF1), following X-irradiation.
  • To determine the relationship between p53 accumulation, p21(sdi1/WAF1) induction, and cell cycle arrest after X-ray exposure.

Main Methods:

  • Analysis of sdi1 mRNA accumulation after X-irradiation in cells with wild-type p53.
  • Quantification of p53 and p21(sdi1/WAF1) protein levels in response to varying doses of X-irradiation.
  • Cell cycle analysis (G1 and S phase populations) following irradiation.

Main Results:

  • X-irradiation induced sdi1 mRNA accumulation and G1 arrest exclusively in cells with wild-type p53.
  • p53 accumulation preceded the elevation of p21(sdi1/WAF1), independent of p53 mRNA levels.
  • Both p53 and p21(sdi1/WAF1) accumulation were radiation dose-dependent and occurred throughout the cell cycle (G0, G1, S phases).
  • A dose-dependent decrease in the S phase population was observed, reaching a minimum at submaximal p53 and p21(sdi1/WAF1) levels.

Conclusions:

  • An X-ray-induced mechanism for p53 and p21(sdi1/WAF1) accumulation operates throughout the cell cycle.
  • The strength of the X-ray-induced signal is directly proportional to the radiation dose.

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