211At-alpha-dose dependence of poly-ADP-ribosylation of human glioblastoma cells in vitro. Suitability in cancer therapy?
OBJECTIVE
It was intended to test the biological response (poly-ADP-ribosylation of cellular proteins) of alpha-particles from extracellular 211At for enhanced damage to human glioblastoma cells in vitro and to discuss its suitability for potential application in therapy of high-grade gliomas.


METHODS
Confluent cultures of human glioblastoma cells were exposed to different doses of alpha-radiations from homogeneously distributed extracellular 211At. Cellular poly-ADP-ribosylation of all proteins including histones was monitored since it is an indirect but sensitive indicator of chromatin damage and putative repair in both normal and malignant mammalian 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 approximately 119.0% at 0.0025 Gy. Below 0.0025 Gy no change in poly-ADP-ribosylation was observed.


CONCLUSIONS
Level of cellular poly-ADP-ribosylation of proteins at 0.025 to 1.0 Gy of alpha-radiation dose from 211At appears to cause enhanced damage by creating molecular conditions which are not conducive to repair of DNA damages in human glioblastoma cells in vitro. Therefore, it is assumed that clinical application of 211At at least in this dose range might enhance clinical efficacy in radiotherapy of cancer.
Schneeweiss
F H
FH
Institut für Medizin, Forschungszentrum Jülich, Germany. f.schneeweiss@fz-juelich.de
Sharan
R N
RN
Brown
I
I
D000512:Alpha Particles; D001246:Astatine / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000532:radiotherapy*; D002868:Chromosomal Proteins, Non-Histone / Q000528:radiation effects*; D004260:DNA Repair / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005909:Glioblastoma / Q000532:radiotherapy*; D006801:Humans; D066298:In Vitro Techniques; D018499:Linear Energy Transfer; D011064:Poly Adenosine Diphosphate Ribose / Q000528:radiation effects*; D011499:Protein Processing, Post-Translational / Q000528:radiation effects; D014407:Tumor Cells, Cultured / Q000528:radiation effects*
D002868:Chromosomal Proteins, Non-Histone; D011064:Poly Adenosine Diphosphate Ribose; D001246:Astatine