Cell cycle progression and apoptosis after irradiation in an acidic environment.
We investigated the effect of an acidic environment on the radiation-induced G2/M arrest and apoptosis using RKO.C human colorectal cancer cells expressing wild-type p53 and RC10.1 cells, a subline of RKO.C cells deficient in p53 as well as p53+/+ MEFs and p53-/- MEFs (mouse embryonic fibroblasts). The cells were irradiated with 4 Gy or 12 Gy of gamma-rays in pH 7.5 medium or pH 6.6 medium. p53 accentuated the progression of cells from radiation-induced G2/M arrest to apoptosis and the pH 6.6 environment suppressed the progression of cells through G2/M-phase to apoptosis after irradiation. Further analysis indicated that the radiation-induced G2/M arrest was due mainly to G2 arrest in both pH 7.5 and pH 6.6. Therefore, it was concluded that p53 enhances, and an acidic environment suppresses, the exit of cells from radiation-induced G2 arrest by altering cyclin B1-Cdc2 kinase activity.
University of Minnesota Medical School, Department of Therapeutic Radiology-Radiation Oncology, Radiation Biology Section, 420 Delaware St. S.E., Box 494 Mayo, Minneapolis, MN 55455, USA.
H J
HJ
Park
J C
JC
Lyons
T
T
Ohtsubo
C W
CW
Song
D000143:Acids; D017209:Apoptosis / Q000528:radiation effects*; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle; D003470:Culture Media; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D053938:DNA Fragmentation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000143:Acids; C534699:CCNB1 protein, human; C493956:CDKN1A protein, human; C534700:Ccnb1 protein, mouse; D003470:Culture Media; D019926:Cyclin B; D056744:Cyclin B1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53; D011065:Poly(ADP-ribose) Polymerases; D016203:CDC2 Protein Kinase