PHORBOL ESTERS CAN PROTECT MOUSE PRE-T CELL-LINES FROM RADIATION-INDUCED RAPID INTERPHASE APOPTOSIS

Protein kinase C stimulators were found to increase the radioresistanc e of the mouse pre-T cell-derived line ST4. Increased resistance to ga mma-ray-induced killing could be produced by addition of 10 nM phorbol 12-myristate 13-acetate (PMA) to ST4 cultures either immediately befo re or up to 2 h after irradiation. Following PMA treatment, ST4 change d from a cell line that underwent rapid interphase apoptosis (i.e. DNA degradation and morphology characteristic of apoptosis were evident 2 -3 h after irradiation) to a line that continued to cycle after irradi ation and began to die by apoptosis after completing mitosis. Associat ed with these PMA-induced changes, the D, of ST4 cells increased from 7.7 +/- 0.7 to 18.8 +/- 2.7 I-125 decays. Another mouse pre-T cell-der ived line, STI, which is susceptible to radiation-induced rapid interp hase apoptosis, also showed radioprotection after PMA treatment. In co ntrast, PMA increased the radiosensitivity of the pre-T cell-derived W 7 line, which undergoes radiation-induced delayed interphase apoptosis (i.e. death following blockage in G(2) phase). PMA had no effect on t he radiosensitivity of a pre-B cell-derived line, A8, which undergoes rapid interphase apoptosis, and on a pre-T cell-derived line, W22, whi ch undergoes apoptosis after mitosis. These results suggest that the r adiomodifying ability of PMA treatment is dependent upon the cell deat h pathway induced by irradiation and upon the cell lineage.