Biomedical subjects
Publications and source records attributed to D C Lloyd.
Specimens of human blood were exposed at specific energy absorption rates of 104 or 193 W kg-1 to 2.45 GHz microwave radiation at temperatures below 36 degrees C. Cultured lymphocytes were examined for induced unstable chromosome and chromatid aberrations and sister chromatid exchanges. The amount of chromosome damage observed did not exceed that found in controls.
Unstable chromosome aberrations induced by in vitro irradiation with D-T neutrons have been analyzed in human blood lymphocytes. With respect to 250 kVp X rays a maximum limiting RBE at low doses of 4.1 was obtained for dicentric aberrations. Using aberrations as markers in mixed cultures of irradiated and unirradiated cells permits an assessment of interphase death plus mitotic delay. The low-dose RBE for this effect is 2.5. Assuming all unstable aberrations observed at metaphase would lead to cell death by nondisjunction allows an assessment of mitotic death. The low-dose RBE for this effect is 4.5. The data are compared with similar work obtained earlier with 242Cm alpha particles. The application of the present work to cytogenetic assessment of dose after accidental exposure to D-T neutrons is discussed.
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In a study comparing two regimens of treatment after intra-articular irradiation of the knee with yttrium-90 one group of patients was allocated to bed rest for 48 hours in hospital and the other to mobilisation at home. Initially a Robert-Jones orthopaedic bandage was applied to the knee in all patients, serving as a semi-rigid splint, but as loss of isotope from the knee was appreciable in the mobilised patients, subsequent patients were sent home with the knee in a plaster-of-Paris cylinder. No difference in extra-articular spread or chromosomal damage was found between the patients sent home with their knee in a rigid splint and those treated by bed rest. Clinical outcome at three months was satisfactory in all three groups. These results show that rigid splinting is essential in reducing extra-articular spread of the isotope but that bed rest is not necessary. Increases in intra-articular pressure associated with quadriceps muscle activity combined with flexion of the knee may be the most important factor affecting extra-articular spread of isotope.
Samples of human peripheral blood were given X-ray doses of 1, 2, 3 or 4 Gy at 37 degrees C with a further sample remaining unirradiated. Lymphocytes were then stimulated to divide in cultures containing BrdU for 40-72 h. After harlequin staining the metaphases were recorded as being in their 1st, 2nd or 3rd post-irradiation division. It was confirmed that irradiation delays the proliferation of lymphocytes in culture. A linear relationship between dose and mitotic delay of approximately 1 h per Gray was obtained. This finding of a small effect on cell proliferation is particularly important for biological dosimetry. All in vivo exposures are more or less non-uniform and the lymphocytes in a blood sample therefore possess a spectrum of induced delay characteristics. However, in the great majority of overdose investigations it should not be necessary to increase the normal culture time for the most highly irradiated cells to reach metaphase. The trend towards using harlequin preparations to ensure that only first-division cells are analysed is briefly discussed and it is noted that in this experiment 2nd-cycle metaphases accounted for a maximum of 14% of the cells scored after 48 h in culture.
Peripheral blood lymphocytes from unirradiated control subjects and workers exposed within permitted limits to gamma-radiation, have been examined for the incidence of dicentric and acentric chromosome aberrations. The results are compared with a review of data published elsewhere. Background levels show inter-laboratory variation and possible reasons for this are discussed. By combining the present data with those from the literature the spontaneous incidence of dicentric aberrations in approx. 0.55 X 10(-3) and for acentrics is 3.7 X 10(-3). In occupationally exposed subjects a significantly higher incidence of aberrations was found. When allowance was made for the turnover of lymphocytes for the period over which each man had worked with radiation a linear dose--effect relationship was apparent. The incidence of dicentrics was 2.22 +/- 0.94 X 10(-4) rad-1 and for all unstable aberrations 8.24 +/- 2.8 X 10(-4) rad-1. These are in reasonable agreement with dose--response data obtained in vitro.
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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 yields of unstable chromosome aberrations induced in human lymphocytes by alpha-particles from plutonium-239 have been measured. Plutonium citrate solution was mixed with heparinized blood so that doses of 13--160 rad were delivered in 24 hours. Dicentric aberration yields (Y) fitted best to the linear expression Y = 3 . 72 +/- 0 . 23 x 10(-3) rad-1. Inclusion of a 6 . 5 rad point resulting from a 1 . 7 hour irradiation raised the yield coefficient insignificantly to 3 . 75 +/- 0 . 24 x 10(-3). The aberration yields are in good agreement with data from curium-242 alpha-particles obtained in this laboratory but they are much lower than those obtained in two other laboratories. Reasons for this disagreement are examined.
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.
An in vitro dose effect curve of dicentric chromosome aberrations in human cord blood lymphocytes has been obtained for 250-kV X-rays. This is compared with a curve prepared in an identical manner using blood from adults. The comparison shows a marginally higher dicentric yield in blood of newborns at doses above about 250 rads.
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In vitro dose--response curves of unstable chromosome aberrations in human lymphocytes have been obtained for 252Cf neutron radiation. The aberration yields fitted best to the linear function Y=aD, which is consistent with the single-track model of aberration formation for high LET radiation. The curves have been compared with others previously produced in this laboratory for several energies of neutrons and for 60Co gamma radiation. The r.b.e. for 252Cf with respect to 60Co is 27 at very low doses, decreasing to 6 at an aberration yield equivalent to 400 rad of 18 rad/hour gamma radiation. A profile of chromosome-aberration induction with depth in a perspex phantom was obtained by placing blood samples at several distances over the range 0.65-2.0 cm from the californium source. This profile was compared with depth-damage calculations for a radium needle. The r.b.e. of 252Cf radiation relative to 226Ra gamma radiation increased with the distance from the source, implying that californium is more effective at greater distances in destroying the ability of cells to divide, which may be an advantage in the treatment of large tumours.
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The extent to which X-ray induced mitotic delay at 150 and 400 rad influences chromosome aberration yields was examined in human peripheral blood lymphocytes. The dicentric was used as a marker and aberrations yields were obtained for mixed cultures prepared from equal numbers of normal and irradiated cells. The cultures were terminated following incubation times of 36-120 h. Greater mitotic delay of the order of a few hours was observed at the higher dose. However most reduction in the number of lymphocytes arriving at metaphase by 48 h may be ascribed to interphase death or failure to transform. Analysis of the dicentric distributions which were expected to follow Poisson statistics indicated that cells containing dicentrics were delayed relative to irradiated but aberration-free cells. Cells with one dicentric moved more easily through the first cell cycle than cells containing two dicentrics. Following accidental partial body irradiation, selection in culture favouring the unirradiated lymphocytes does not distort the aberration yield sufficiently to warrant incubation times in excess of the standard 48-52 h.
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