APOPTOSIS INDUCED BY X-RAYS AND CHEMICAL-AGENTS IN MURINE FIBROBLASTIC CELL-LINES WITH A DEFECT IN REPAIR OF DNA DOUBLE-STRAND BREAKS

Purpose: To investigate apoptosis in murine fibroblasts that are defic ient in DNA double-stand breaks (dsb) repair. Materials and methods: B ALB/c 3T3 cells and cells from a severe combined immunodeficient (scid ) mouse were exposed to X-rays, UV light, bleomycin, etoposide or cisp latin. After exposure, the rate of apoptosis was assayed by propidium iodide staining based on characteristic morphological change. Results: The scid cells, defective in dsb repair, were extremely sensitive to apoptosis induced by X-rays and bleomycin compared with BALB/c 3T3 cel ls. The scid cells were slightly sensitive to apoptosis induced by eto poside, an agent producing protein-associated dsb, and to apoptosis in duced by agents not causing dsb. Conclusions: These studies show that sensitivity of cells to apoptosis induced by X-rays or bleomycin is en hanced by the scid mutation and that apoptosis induced by etoposide, w hich causes protein-associated dsb, is not greatly affected. There may be different processes involved in the induction of apoptosis by X-ra ys or bleomycin and etoposide.