Cell cycle progression and apoptosis after irradiation in an acidic environment

We investigated the effect of an acidic environment on the radiation-induce d G2/M arrest and apoptosis using RKO.C human colorectal cancer cells expre ssing 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 fibroblast s). The cells were irradiated with 4 Gy or 12 Gy of gamma-rays in pH 7.5 me dium or pH 6.6 medium. p53 accentuated the progression of cells from radiat ion-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 .