At-211-alpha-dose dependence of poly-ADP-ribosylation of human glioblastoma cells in vitro - Suitability in cancer therapy?

Aim: It was intended to test the biological response (poly-ADP-ribosylation of cellular proteins) of a-particles from extracellular At-211 for enhance d damage to human glioblastoma cells in vitro and to discuss its suitabilit y for potential application in therapy of high-grade gliomas. Materials and Methods : Confluent cultures of human glioblastoma cells were exposed to different doses of a-radiations from homogeneously distributed extracellular At-211. Cellular poly-ADP-ribosylation of all proteins includ ing histones was monitored since it is an indirect but sensitive indicator of chromatin damage and putative repair in both normal and malignant mammal ian cells. Results: A significant diminution (average 85.6%) in poly-ADP-ribosylation of total cellular proteins relative to that for non-irradiated glioblastoma cells was observed following 0.025 to 1.0 Gy alpha-radiations. In the dose range of 0.0025 to 0.01 Gy there was an increase with a maximum value of a pproximately 119.0% at 0.8025 Gy. Below 0.0025 Gy no change in poly-ADP-rib osylation was observed. Conclusions: Level of cellular poly-ADP-ribosylation of proteins at 0.025 t o 1.0 Gy of alpha-radiation dose from At-211 appears to cause enhanced dama ge by creating molecular conditions which are not conducive to repair of DN A damages in human glioblastoma cells in vitro. Therefore, it is assumed th at clinical application of At-211 at least in this dose range might enhance clinical efficacy in radiotherapy of cancer.