Delayed lethality, apoptosis and micronucleus formation in human fibroblasts irradiated with X-rays or alpha-particles

Purpose: To determine the yields of cell lethality and micronucleus formati on measured immediately after irradiation or at delayed times in primary hu man fibroblasts exposed to X-rays or alpha-particles. Materials and methods: Primary human AG01522B fibroblasts were irradiated w ith X-rays or alpha-particles and subcultured for up to 30 days post-irradi ation. Clonogenic survival and the yield of micronucleated cells in newly d ivided daughter cells were scored at various times. Results: After the initial dose-dependent acute response for both endpoints there was conclusive evidence for the delayed production of de novo genomi c instability in the surviving progeny. As well as the production of micron ucleated cells, evidence was observed for the production of fibroblasts und ergoing apoptosis as measured using conventional morphological scoring, 3'O H end-labelling of DNA fragmentation and externalization of phosphatidyl se rine residues to the cell surface. For both radiations, the dose and time d ependencies of the apoptotic response were similar to those for micronuclea tion and loss of clonogenicity. Conclusions: Genomic instability in the progeny of irradiated primary human fibroblasts vias observed in the form of micronucleation, apoptosis and de layed reproductive death. An increased effectiveness of alpha-particles ver sus X-rays was observed for both initial and delayed responses, including a poptosis.