Radiation-induced apoptosis in the adult central nervous system is p53-dependent.
Oligodendrocytes and subependymal cells in the adult CNS have been shown to undergo radiation-induced apoptosis. Here, we examined the role of p53 in radiation-induced apoptosis in the adult mouse CNS. In the spinal cord of p53+/+ mice, apoptotic glial cells were observed within 24 h after irradiation, and the apoptotic response peaked at 8 h. These apoptotic cells demonstrated the immunohistochemical phenotype of oligodendrocytes, and decreased oligodendrocyte density was observed at 24 h after 22 Gy. A similar time course of radiation-induced apoptosis was seen in subependymal cells in the adult mouse brain. Radiation-induced apoptosis was preceded by an increase in nuclear p53 expression in glial cells of the spinal cord and subependymal cells of the brain. There was no evidence of radiation-induced apoptosis in the spinal cord and subependymal region of p53-/- animals. We conclude that the p53 pathway may be a mechanism through which DNA damage induces apoptosis in the adult CNS.
Division of Experimental Therapeutics, Ontario Cancer Institute, Department of Medical Biophysics, University of Toronto, Toronto, Canada.
B M
BM
Chow
Y Q
YQ
Li
C S
CS
Wong
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D002452:Cell Count; D002490:Central Nervous System / Q000166:cytology / Q000528:radiation effects*; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000166:cytology / Q000528:radiation effects; D009836:Oligodendroglia / Q000166:cytology / Q000528:radiation effects; D051381:Rats; D011916:Rats, Inbred F344; D013116:Spinal Cord / Q000166:cytology / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*
D016159:Tumor Suppressor Protein p53