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 deficient in DNA double-stand breaks (dsb) repair. MATERIALS AND METHODS: BALB/c 3T3 cells and cells from a severe combined immunodeficient (scid) mouse were exposed to X-rays, UV light, bleomycin, etoposide or cisplatin. 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 cells. The scid cells were slightly sensitive to apoptosis induced by etoposide, an agent producing protein-associated dsb, and to apoptosis induced by agents not causing dsb. CONCLUSIONS: These studies show that sensitivity of cells to apoptosis induced by X-rays or bleomycin is enhanced by the scid mutation and that apoptosis induced by etoposide, which causes protein-associated dsb, is not greatly affected. There may be different processes involved in the induction of apoptosis by X-rays or bleomycin and etoposide.