Importance of DNA damage in the induction of apoptosis by ionizing radiation: effect of the scid mutation and DNA ploidy an the radiosensitivity of murine lymphoid cell lines

Purpose: To study the effects of the murine scid mutation and DNA ploidy on the susceptibility of lymphoid cell lines to induction of apoptosis by ion izing radiation and thereby to determine whether DNA lesions are critical i nitiators of apoptosis. Materials and methods: Sensitivity to killing and rapidity of induction of apoptosis following gamma-irradiation or DNA-associated I-125 decays were c ompared in pre-B and pre-T cell lines derived from wild-type mice and from mice homozygous or heterozygous for the scid mutation, Effects of differenc es in DNA ploidy on the same endpoints were studied using pseudo-diploid an d -tetraploid clones of a murine pre-T cell line. Results: Pairs of pre-B- and pre-T cell-derived lines that expressed wild-t ype p53 and underwent rapid interphase apoptosis after irradiation were ide ntified. In both cases, the scid homozygous cell lines were more sensitive to killing, suggesting that DNA repair capability influences susceptibility to induction of apoptosis, Increasing DNA ploidy in a cell line that under goes rapid interphase apoptosis produced a corresponding increase in the nu mber of DNA lesions required to produce a lethal event; again consistent wi th DNA being the target for radiation action. Conclusion: DNA damage is an important, if not the sole, initiator of exter nal beam ionizing radiation-induced apoptosis.