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.

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.

In vitro dose--response curves of unstable chromosome aberrations in human lymphocytes have been obtained for neutron spectra of mean energies 0-7, 0-9, 7-6 and 14-7 MeV. The aberration yields have been fitted to the quadratic function Y = alphaD + betaD2, which is consistent with the single-track and two-track model of aberration formation. However with high-LET radiation, the linear component of yield, corresponding to damage caused by single tracks, predominants, and this term becomes more dominant with increasing LET, so that for fission spectrum neutrons the relationship is linear, Y = alphaD. At low doses, such as those recieved by radiation workers, limiting r.b.e. values between 13 and 47 are obtained relative to 60Co gamma-radiation. At higher doses, as used in radiotherapy, the values are much lower; ranging from 2-7 to 8 at 200 rad of equivalent gamma-radiation. Both sets of r.b.e. values correlate well with track-averaged LET but not with dose-averaged LET. When the numbers of cells without aberrations are plotted against radiation dose, curves are obtained which are similar in shape to those for conventional cell-survival experiments with comparable neutron spectra. The Do values obtained in the present study are close to those from other cell system.

The form of the killing curve obtained by bombaring micro-organisms with high energy electrons enables an estimate to be made of the numbers of individual viable organisms present in the aggregates or clumps comprising the sample. Samples of Staph. aureus collected from the air of two hospital wards have been found to consist of aggregates containing, on the average, only about four viable cocci per air-borne particle. These samples were taken during quiet periods and during periods of active dispersion of the organism but there was no active spread of staphylococcal disease at any time.The work on the linear accelerator was carried out with the aid of grants provided by the Treasurer and the Board of Governors from the Discretionary Fund of St Bartholomew's Hospital, to whom we wish to express our gratitude.

An account of the chromosome damage found in the lymphocytes of thirteen patients who had received injections of gold-198 into knee joints was reported in a preliminary communication (Stevenson, Bedford, Hill, and Hill, 1971a). There were great differences in the amount of damage which followed injections of the same amount of activity in these patients. However, the mean level of damage appeared too high to be explained by the assumption either that it occurred as a result of irradiation of lymphocytes in the injected joint, or that the radionuclide was distributed throughout the whole body, for the average radiation dose to the body would only be about 0 5 rad from the gamma radiation per mCi of gold-198. It was suggested that the high level of chromosome damage in lymphocytes relative to the amount of activity injected was most probably due to the movement of gold from the knee along the lymphatics to the inguinal lymph nodes, where enormous numbers of lymphocytes in transit through the nodes would come within the range of the beta emission of the radionuclide.Many patients have been treated with benefit by gold-198 or yttrium-90 intra-articular injections (Ansell, Crook, Mallard, and Bywaters, 1963;Delbarre, Cayla, Menkes, Roucayrol, Ingrand, and Aignan, 1969; Bridgnan, Bruckner, and Bleehen, 1971), and it seemed important to try to assess more accurately the amount of chromosome damage in lymphocytes in order to attempt to elucidate the prognostic significance, if any, to patients from these procedures. For this reason, and because there is very little available information on the cytogenetic effects of parenterally-administered radioactive isotopes in man, it was decided to investigate further cases.Including those reported in the preliminary paper, 48 patients who have had gold-198 injections, and 22 who have had yttrium-90 injections have now been investigated. None of these patients received any external radiotherapy. As the appendices show, blood samples from some patients were not taken until several months or years after the injections. Some were taken both before and at intervals after treatment, and some patients were scanned after injection in order to determine the distribution of the isotopes.The colloidal gold-198 (half life 65 hrs) and yttrium-90 (half life 64 hrs) were obtained from the Radiochemical Centre, Amersham, catalogue numbers GCS1P and YAS3P respectively.The gold preparation is a colloidal suspension of metallic gold stabilized with gelatin and with particle sizes of up to 20 pm. Most of the activity is in the 10-13 pm particles. The yttrium preparation is ionic yttrium bound to a colloidal ion exchange resin with a particle size range from 20 to 50 pum.