Abstract
Purpose
The dose-response relationship and the relative biological effectiveness (RBE) for the induction of micronuclei in lymphocytes was analyzed after irradiation in vitro with a 6-MeV neutron beam that was followed by 240-kV X-rays. The dose range of the combined exposure comprised 1 to 3 Gy. For reference, the dose-effect relationships found after X-ray (0.5 to 5 Gy)-and neutron (0.5 to 4 Gy) exposure applied separately are presented. The possibility of an interaction between the 2 radiation qualities is investigated by the method of isobole calculation termed “envelope of additivity”.
Methods
Micronuclei were analyzed in PHA-stimulated, cytokinesis-blocked human lymphocytes.
Results
The dose-response relationships for the micronucleus frequencies induced by the neutron irradiation, as well as by the mixed exposure, were linear. A saturation effect was indicated after neutron doses higher than 3 Gy. After low LET exposure the dose-response curves were describable by a linear-quadratic model. For neutron-induced micronucleus frequencies, RBE-values of 2 to 3 and for the combined exposure RBE values of 1.5 to 2 were calculated for a range of effect of 0.5 to 1.5 micronuclei/binucleated lymphocyte. No indication was found for an interaction between the damage induced by X-rays and that produced by neutrons under our experimental conditions.
Conclusions
These studies demonstrate a clear dependence of micronucleus induction on radiation quality and empha-size the usefulness of the micronucleus assay in biological dosimetry, also in cases in which high LET radiation or a mixed beam is involved as the radiation source.
Zusammenfassung
Fragestellung
Die Mikronukleusinduktion in Lymphozyten wurde nach In-vitro-Bestrahlung mit 6-MeV-Neutronen (0,5 bis 4 Gy), 240-kV-Röntgenstrahlung (0,5 bis 5 Gy) bzw. einer Kombination dieser Strahlenqualitäten (1 bis 3 Gy Gesamtdosis) untersucht. Anhand der Dosis-Wirkungs-Beziehungen für die einzelne und kombinierte Anwendung beider Strahlenarten wurde die relative biologische Wirksamkeit (RBW) für Neutronen bzw. für die Kombination von Neutronen und Röntgenstrahlen ermittelt. Mit Hilfe einer Isobolenkalkulation (“envelope of additivity”) wurde die Möglichkeit einer Interaktion zwischen den beiden Strahlenqualitäten analysiert.
Methode
Die Auswertung der Mikronuklei erfolgte in PHA-stimulierten humanen Lymphozyten, deren Zytokinese durch Cytochalasin B inhibiert worden war.
Ergebnisse
Für die Neutronen-wie auch für die kombinierte Bestrahlung ergaben sich jeweils lineare Dosis-Wirkungs-Beziehungen. Ein Sättigungseffekt stellte sich für Neutronendosen oberhalb von 3 Gy ein. Nach Niedrig-LET-Bestrahlung folgte die Dosis-Wirkungs-Beziehung dem linear-quadratischen Modell. Ein Vergleich der für die Induktion von 0,5 bis 1,5 Mikronuklei pro binukleärer Zelle isoeffektiven Dosen ergab für die Bestrahlung mit Neutronen RBW-Werte von 2 bis 3 und für die kombinierte Bestrahlung Werte von 1,5 bis 2 unter den von uns gewählten experimentellen Bedingungen. Es konnte kein Hinweis auf eine Interaktion zwischen den durch die Röntgen-bzw. Neutronenstrahlung induzierten Schäden gewonnen werden.
Schlußfolgerungen
Die Untersuchungen zeigen eine deutliche Abhängigkeit der Mikronukleusbildung von der Strahlenqualität. Die Ergebnisse verdeutlichen, daß der Einsatz des Mikronukleusassays in der biologischen Dosimetrie auch dann sinnvoll ist, wenn als Strahlenquelle eine Hoch-LET-Strahlung bzw. eine Mischung aus Hoch-und Niedrig-LET-Strahlen vorliegt.
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Wuttke, K., Müller, WU. & Streffer, C. The sensitivity of the in vitro cytokinesis-blocked micronucleus assay in lymphocytes for different and combined radiation qualities. Strahlenther Onkol 174, 262–268 (1998). https://doi.org/10.1007/BF03038719
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DOI: https://doi.org/10.1007/BF03038719