INCREASE OF INTRACELLULAR PH IN P53-DEPENDENT APOPTOSIS OF THYMOCYTESINDUCED BY GAMMA-RADIATION

Irradiation with gamma rays induces apoptosis of thymocytes by a p53-d ependent pathway, but its mechanism is not clear. In this study, we re port that gamma-ray-induced apoptosis was associated with the intracel lular alkalinization of the thymocytes. After exposure to gamma rays, thymocytes underwent apoptosis when cultured in vitro, and the degree of apoptosis was dependent on the incubation period: The longer the in cubation period, the greater the number of cells undergoing apoptosis. However, this apoptosis could be inhibited by the acidic condition of the culture. There was a positive correlation between the pH(i) of th ymocytes and the degree of apoptosis. Treatment with gamma radiation i nduced apoptosis as well. as the elevation of the pH(i) in thymocytes. The intracellular pH was higher in pre-apoptotic thymocytes than in t hose that did not undergo apoptosis. Furthermore, apoptosis induced by gamma radiation was inhibited by cycloheximide, actinomycin D or the intracellular Ca2+ chelator, TMB-8. The p53 protein is induced after g amma irradiation. Thus it appears that intracellular pH is increased d uring the gamma-ray-induced p53-dependent apoptosis of thymocytes. (C) 1998 by Radiation Research Society.