HBO and the uptake and retention of [125I] MIBG in human platelets and two neuroendocrine cell lines.

In this paper we report the effects of Hyperbaric Oxygen (HBO) exposure on the uptake and retention of meta-Iodobenzylguanidine (MIBG) in human platelets and two neuroendocrine cell lines. The combination of [131I] MIBG and HBO is used for therapy of neuroblastoma. Exposure to HBO can cause oxidative stress, which is potentially capable of affecting uptake and storage of MIBG in both neuroendocrine cells and platelets. Oxidative stress generated by menadione decreased both the uptake and retention of MIBG in the platelets and the cell lines. HBO did not affect these processes, indicating that the HBO induced oxidative stress is not high enough to affect the MIBG uptake and storage pathways in these cells. This suggests that the positive effects observed by the treatment of neuroblastoma patients with the combination of HBO and [131I] MIBG are most likely not due to improved uptake or retention of MIBG in the neuroblastoma. Neither can reduced cytotoxicity (trombocytopenia) be expected due to decreased uptake/retention of [131I] MIBG in platelets or their precursor cells.

Menadione inhibits MIBG uptake in two neuroendocrine cell lines.

In this paper we report on our studies of the effect of menadione on the uptake of MIBG in the neuroendocrine cell lines PC12 and SK-N-SH. Menadione inhibits the uptake of MIBG in both cell lines in a dose-dependent manner. Inhibition of MIBG uptake is most pronounced in the PC12 cell line. Comparison of the inhibitory action of menadione on the uptake and retention of MIBG with that of imipramine and reserpine suggests that menadione inhibits uptake 1 mediated uptake as well as granular storage.

Use of fluorescence in situ hybridization to measure chromosome aberrations as a predictor of radiosensitivity in human tumour cells.

Fluorescence in situ hybridization (FISH) is a potential assay for determining cellular radiosensitivity based on the detection of chromosome damage. This approach was chosen because of its relative simplicity and short assay time. Two radiosensitive and two radioresistant human tumour cell lines were used. The radiosensitive lines were an ovarian carcinoma line (A1847) and a squamous carcinoma line (SCC61). The radioresistant cells were a lung adenocarcinoma line (A549) and a second squamous line (SQ20B). Whole chromosome-specific probes were used to detect radiation-induced chromosome aberrations in mitotic cells. Available probes were first screened to characterize the intrinsic chromosome aberrations before irradiation and the appropriate probes (minimum fluorescent spots) were selected for each cell line. Maximum radiation-induced aberrations were found 24 h after irradiation. Dose-response curves corrected for target size (proportion of genome probed) differed for all cell lines. The radiosensitive A1847 cell line showed more induced aberrations compared with the radioresistant A549 cell line, in agreement with the survival data. In contrast, the SQ20B cell line showed more induced chromosome aberrations than the more radiosensitive SCC61 cell line, leading to the hypothesis that the SQ20B cells could tolerate more aberrations. Dose-response curves obtained in surviving cells 14 days postirradiation indeed showed elevated levels of chromosome aberrations for SQ20B cells. The difference in chromosome aberrations between 1 and 14 days showed a good correlation with the survival data for all four cell lines. In conclusion, FISH of mitotic cells with whole chromosome probes appears to be a suitable assay to predict radiosensitivity. It seems necessary, however, to determine both induced and remaining chromosome aberrations, since different processing or tolerance of radiation-induced aberrations, including stable types, could lead to different correlations with cell survival.