[CITATION][C] Age‐related changes in irradiation‐induced apoptosis and expression of p21 and p53 in crypt stem cells of murine intestine

K Martin, CS Potten… - Annals of the New York …, 2000 - Wiley Online Library
K Martin, CS Potten, TBL Kirkwood
Annals of the New York Academy of Sciences, 2000Wiley Online Library
DISCUSSION These results showed that a clear alteration in the apoptotic response to
ionizing radiation occurs with age in the mouse intestinal crypt cells. Crypt stem cells from
older mice were more sensitive to irradiation, suggesting an alteration with age in the
regulation of the pathway responsible for detection of damage and the decision between
repair and in induction of cell death. p53 expression has been described as playing a key
role in the induction of apoptosis following exposure to ionizing radiation. 3, 4, 6 p53 …
DISCUSSION
These results showed that a clear alteration in the apoptotic response to ionizing radiation occurs with age in the mouse intestinal crypt cells. Crypt stem cells from older mice were more sensitive to irradiation, suggesting an alteration with age in the regulation of the pathway responsible for detection of damage and the decision between repair and in induction of cell death. p53 expression has been described as playing a key role in the induction of apoptosis following exposure to ionizing radiation. 3, 4, 6 p53 expression correlated with the first wave of apoptosis, whereas the second wave was p53-independent. p53 inhibits cell-cycle progression (via p21) while damaged DNA is repaired. If the damage is too extensive, p53 may induce apoptosis. 7 The delayed p53 expression in older animals implies a delay in DNA damage screening and repair, which is in accordance with the delayed expression of p21. Unrepaired cells that escaped from the first apoptosis peak may continue to progress into S phase, and they would reach the G 2/M checkpoint with DNA damage. The elevated first apoptotic peak and the presence of a second peak at 24 hours, together with the delayed expression of both p53 and p21, clearly reveal an alteration in the cellular response to injury in the murine intestinal crypts in older mice.
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