Production of delayed death and neoplastic transformation in CGL1 cells byradiation-induced bystander effects

Other investigators have demonstrated by transfer of medium from irradiated cells and by irradiation with low-fluence a particles or microbeams that c ells do not have to be directly exposed to ionizing radiation to be detrime ntally affected, i.e. bystander effects. In this study, we demonstrate by t ransfer of medium from X-irradiated human CGL1 hybrid cells that the killin g of bystander cells reduces the plating efficiency of the nonirradiated CG L1 cells by 33 +/-6%. In addition, we show that the amount of cell death in duced by bystander effects is not dependent on X-ray dose, and that the ind uction of apoptosis does not appear to be responsible for the cell death. F urthermore, we found that the reduction in plating efficiency in bystander cells is evident for over 18 days, or 22 cell population doublings, after m edium transfer, despite repeated refeeding of the cell cultures. Finally, w e report the novel observation that bystander effects induced by the transf er of medium from irradiated cells can induce neoplastic transformation. Ex posing unirradiated CGL1 cells to medium from cells irradiated with 5 or 7 Gy increased the frequency of neoplastic transformation significantly from 6.3 x 10(-6) in unirradiated controls to 2.3 x 10(-5) (a factor of nearly f our). We conclude that the bystander effect induces persistent, long-term, transmissible changes in the progeny of CGL1 cells that result in delayed d eath and neoplastic transformation. The data suggest that neoplastic transf ormation in bystander cells may play a significant role in radiation-induce d neoplastic transformation at lower doses of X rays. (C) 2001 by Radiation Research Society.