In vitro radiosensitizing effects of ultrasmall gadolinium based particles on tumour cells.

Since radiotherapy is widely used in cancer treatment, it is essential to develop strategies which lower the irradiation burden while increasing efficacy and become efficient even in radio resistant tumors. Our new strategy is relying on the development of solid hybrid nanoparticles based on rare-earth such as gadolinium. In this paper, we then evidenced that gadolinium-based particles can be designed to enter efficiently into the human glioblastoma cell line U87 in quantities that can be tuned by modifying the incubation conditions. These sub-5 nm particles consist in a core of gadolinium oxide, a shell of polysiloxane and are functionalized by diethylenetriaminepentaacetic acid (DTPA). Although photoelectric effect is maximal in the [10-100 keV] range, such particles were found to possess efficient in-vitro radiosensitizing properties at an energy of 660 keV by using the "single-cell gel electrophoresis comet assay," an assay that measures the number of DNA damage that occurs during irradiation. Even more interesting, the particles have been evidenced by MTT assays to be also efficient radiosensitizers at an energy of 6 MeV for doses comprised between 2 and 8 Gy. The properties of the gadolinium-based particles give promising opening to a particle-assisted radio-therapy by using irradiation systems already installed in the majority of hospitals.

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

PURPOSE: To investigate the relationship between the susceptibility of B-chronic lymphoid leukaemia (B-CLL) 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 B-CLL patients were gamma-irradiated in vitro with 0.2-5 Gy and stimulated by Staphylococcus aureus cowan I (SAC I) for estimation of chromosomal damage. Induction of apoptosis after irradiation was studied in 50 patients 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 patients). In parallel, the kinetics of DNA single-strand break rejoining were investigated by the alkaline comet assay (12 patients). RESULTS: Ionizing irradiation did not induce apoptosis in lymphocytes from a subset of B-CLL patients. The results suggest that B-CLL cells resistant to radiation-induced apoptosis could repair DNA strand-breaks more rapidly and showed a higher level of chromosome aberrations than radiation-sensitive B-CLL 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 B-CLL 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.

Antibody-dependent Fos-like immunoreactivity (FLI) in the auditory pathway of the rat in response to electric stimulation of the cochlea.

The distribution of Fos-like immunoreactivity (FLI) in the auditory pathway was analyzed and quantified in two groups of rats subjected to a similar electric stimulation of the cochlea, but the brains of the two groups were treated with a different antibody against Fos. The brains of control (unstimulated) rats were processed and analyzed in the same way. In a given auditory nucleus, for the same paradigm of stimulation, a very different density of FLI can be found depending on the antibody used to process the tissue. There are auditory nuclei which exhibited a significant activation of FLI as compared to control animals when one antibody was used whereas there was no difference when using the other antibody. In other cases, for both antibodies, a significant FLI increase was observed in relation to the stimulus. However, the increase of FLI density was significantly greater in some auditory nuclei with one antibody, while it was the reverse in other auditory nuclei. The present data demonstrate quantitatively that the use of two different Fos antibodies can strongly affect the FLI produced in the auditory pathway by electric stimulation of the cochlea, confirming previous qualitative observations based on acoustic stimulation of the cochlea.