High levels of chromosome aberrations correlate with impaired in vitro radiation-induced apoptosis and DNA repair in XXXX B-chronic lymphocytic leukaemia cells.

@entity1 @entity794 @entity1072
PURPOSE: To investigate the relationship between the susceptibility of @entity1072 ( @entity1072 ) cells to DNA damage-induced apoptosis, the kinetics of DNA strand-break rejoining, and chromosome damage after exposure to ionizing irradiation. MATERIALS AND METHODS: Lymphocytes from @entity1072 @entity1 were gamma-irradiated in vitro with 0.2-5 Gy and stimulated by @entity794 cowan I (SAC I) for estimation of chromosomal damage. Induction of apoptosis after irradiation was studied in 50 @entity1 by two methods: morphological characterization of apoptotic cells after fluorescent staining (Hoechst), and specific quantification of mono- and oligonucleosomes in cytoplasmic cell fractions (ELISA assay). Morphological chromosome damage was scored in the first cell generation after irradiation (13 @entity1 ). In parallel, the kinetics of DNA single-strand break rejoining were investigated by the alkaline comet assay (12 @entity1 ). RESULTS: Ionizing irradiation did not induce apoptosis in lymphocytes from a subset of @entity1072 @entity1 . The results suggest that @entity1072 cells resistant to radiation-induced apoptosis could repair DNA strand-breaks more rapidly and showed a higher level of chromosome aberrations than radiation-sensitive @entity1072 cells. CONCLUSION: Each of three biological effects observed (apoptosis, kinetics of DNA single-strand-break repair, chromosomal damage) might be explained by different modifications occurring in irradiated @entity1072 cells. Their convergence strongly suggests that resistance to apoptotic death initiation by DNA damage may be impeded by a rapid engaging of the DNA repair mechanisms. The higher level of chromosome aberrations observed in these cells suggests that the type of DNA repair system involved may generate inaccurate repair.
