Phorbol esters can protect pre-T cell lines from radiation-induced rapid interphase apoptosis

Protein kinase C stimulators were found to increase the radioresistance of the mouse pre-T cell-derived line ST4. Increased resistance to γ-ray-induced killing could be produced by addition of 10 nM phorbol 12-myristate 13-acetate (PMA) to ST4 cultures either immediately before or up to 2 h after irradiation. Following PMA treatment, ST4 changed 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 irradiation and began to die by apoptosis after completing mitosis. The results suggest that the radiomodifying ability of PMA treatment is dependent upon the cell death pathway induced by irradiation and upon the cell lineage. (author)