Variation in radiosensitivities of different individuals to high energy neutrons and 60Cobalt γ-rays

[摘要] ENGLISH ABSTRACT: Background: The assignment of radiation weighting factors to high energy neutronsources is important as there is reason to believe that neutron relative biologicaleffectiveness (RBE) may be related to the inherent radiosensitivity of differentindividuals. A study was undertaken to quantify the inherent radiosensitivities oflymphocytes obtained from different donors to 60Co y-rays and p(66)/Be neutrons.For this a novel semi-automated image analysis process has been employed. Inaddition the responses of lymphocytes with different inherent radiosensitivities havealso been tested using Auger electrons emitted by 123I.Methods: The RBE of neutrons was determined from dose-response curves forlymphocytes from different donors. Isolated T-lymphocytes irradiated in vitro werecultured to induce micronuclei in binucleated cells and micronuclei (MN) formationsnumerated using a semi-automated Metafer microscope system. The accuracy inobtaining dose response curves with this method has been tested by evaluatingdispersion parameters of MN formations in the response to the different treatmentmodalities. Differences in the inherent radiosensitivities of cells from different donorswere ascertained using 95 % confidence ellipses. [123I]Iododeoxyuridine wasprepared in a formulation that allows incorporation of 123I into the DNA oflymphocytes. Micronucleus formations to this treatment were evaluated inlymphocytes with established differences in inherent radiosensitivities.Results: The image analysis system proved to be consistent in detecting micronucleifrequencies in binucleated lymphocytes. As a result, differences in the inherentradiosensitivities of different individuals were distinctive and could be stated at the95% confidence level. The inter-individual radiosensitivity variations wereconsiderably smaller for blood cells exposed to high energy neutrons compared to60Coy-rays. Relative biological effectiveness (RBEM) values between 2 and 13 were determined that are highly correlated with the inherent radioresistance oflymphocytes obtained from different individuals. As such radiation weighting factorsfor high energy neutrons cannot be based on cytogenetic damage determined inlymphocytes from a single donor. Dispersion parameters for micronuclei formations proved to vary according to ionization density. The variation in RBE with neutrondose changed according to theoretical considerations and automated image analysisdetection of MN is thus a suitable method to quantify radiation weighting factors.A clear reduction in the variation in radiosensitivity is noted for lymphocytes exposedto Auger electrons compared to 60Coy-rays. The effectiveness of Auger electronsfrom [123I]IUdR to induce biological damage is demonstrated as the number of disintegrations needed to yield micronuclei formations was found to be more thantwo orders of magnitude less than that of other compounds. An increase in the RBEof Auger electrons with radioresistance can be inferred from these findings andconstitutes a basis for therapeutic gain in treating cells compared to usingradioisotopes emitting low-LET radiation.

[发布机构] Stellenbosch University