Production of a signal by irradiated cells which leads to a response in unirradiated cells characteristic of initiation of apoptosis

This study investigated the ability of medium from irradiated cells to indu ce early events in the apoptotic cascade, such as mobilization of intracell ular calcium, loss of mitochondrial membrane potential and increase in reac tive oxygen species, in cells which were never exposed to radiation. Medium from irradiated human keratinocytes was harvested and transferred to unirr adiated keratinocytes. Endpoints characteristic of the initiation of apopto sis were monitored for a period of 24 h following medium transfer. Clonogen ic survival was also measured. Rapid calcium fluxes (within 30 s), loss of mitochondrial membrane potential, increases in reactive oxygen species (fro m 6 h after medium transfer), an increase in the number of apoptotic cells (48 hours after medium transfer) and a marked reduction in clonogenic survi val (after 9 days) were observed. There was no significant difference betwe en medium generated by cells irradiated at 0.5 Gy or 5 Gy. The data suggest that initiating events in the apoptotic cascade were induced in unexposed cells by a signal produced by irradiated cells. (C) 2000 Cancer Research Ca mpaign.