Data on the distribution of dicentrics and acentrics observed when human lymphocytes are cultured for 48 h after irradiation by X-rays, gamma-rays, and neutrons are presented. Analysis shows that for dicentrics, the observed distribution for X-rays, gamma-rays, and fission neutrons may be described by Poisson statistics but for higher energy neutrons overdispersion is observed. The phenomenon of overdispersion is also observed for acentrics irrespective of the radiation used. The possibility that overdispersion results from the variations of dose in sensitive sites leads to the conclusion that for dicentrics the site size is considerably larger than the 1--2 micrometer diameter derived by applying the dual action theory to the dose effect relationships. This larger site may well be the cell nucleus.
In vitro dose-response curves of unstable chromosome aberrations in human lymphocytes have been obtained for 250 kV X-rays and cobalt-60gamma-radiation. The aberration yields have been fitted to the quadratic function Y = alphaD +betaD2, which is consistent with the single-track and two-track model for aberration formation. The values of the coefficients alpha and beta support the hypothesis that the dose-rate effect is limited to the D2 term. The main difference between the coefficients for X- and gamma-radiation is in the alpha values, indicating that X-rays are slightly more efficient, at lower doses, in producing two lesions with a single ionizing track. The lower limits of dose estimate, with 500 cells analysed, are 4 rad for X-rays and 10 rad gamma-radiation. Further evidence is presented confirming that, for cytogenetic dosimetry, in vitro dose-response curves should be prepared by irradiating whole blood maintained at 37 degrees C and prior to PHA stimulation. Curves were plotted showing the variation of the number of cells without aberrations with radiation dose and the shape of these curves were compared with those from human cell survival experiments.
Human blood has been irradiated with alpha-particles from an external source of curium-242. The collimated alpha-particles entered the blood with an energy of 4-9 MeV and were almost completely absorbed by the blood. After culturing for 48 hours, the dicentric yield in the lymphocytes at the first metaphase was measured as a function of dose to the blood. The yield was linear with dose up to 400 rad with a slope of 28x6 X 10(4) dicentrics/cell per rad. This is equivalent to an initial slope r.b.e. of 17x9 with respect to cobalt-60 gamma-rays. This value disagrees with the only two other published values in the literature. Reasons for this disagreement are discussed. Compared with neutron r.b.e values obtained in this laboratory the alpha-particle values we observe are surprisingly low. A model is proposed which predicts low values of r.b.e. for chromosome aberration production using radiations of high LET. The low values occur because there is a distribution of specific energy between cells which causes a selective removal of cells likely to contain higher numbers of aberrations.
The effect of X-irradiation on the yield of transformed cells in culture has been studied in human peripheral blood lymphocytes. Aberration yields were obtained for mixed cultures prepared from equal numbers of normal and irradiated lymphocytes and from pure cultures of irradiated cells. Comparison of data from these two types of culture showed that the observed yield ranged from 90% of the expected at 50 rad to 11 at 700 rad. Poisson analysis demonstrated that for all doses, cells with high levels of chromosome structural damage were not selectively eliminated. No attempt has been made to distinguish between the individual effects of interphase death and mitotic delay.Analysis of the aberration yield data demonstrated an approximately dose squared relationship for dicentrics. With acentrics, however, the yield is best represented by a quadratic Y = aD + bD2 expression with the a D term being greater at doses below 100 rad.A D,, value of 270 rad was obtained and is consistent with a target size comparable with that of a chromosome.The implication of this work in the field of dose estimation by chromosome aberration analysis is discussed.
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