The relative biological effectiveness of fractionated doses of fast neutrons (42 MeVd----Be) for normal tissues in the pig. II. Late effects on cutaneous and subcutaneous tissues.

The late effects of irradiation with single and fractionated doses of X rays (250 kV) and fast neutrons (42 MeVd----Bc), on the cutaneous and subcutaneous tissues of the pig, have been evaluated from measurements of changes in relative field length. These were determined at intervals of 26-104 weeks after irradiation. For fractionated irradiation with X rays the average fractions exponent, N, obtained from a log-log plot of iso-effect dose (ED50) against fraction number was 0.41. This was independent of the period of assessment, with no significant indication of a time factor. However, the exponent N did vary with the level of effect and was in the range 0.33-0.51. It was greatest for a greater than or equal to 10% reduction in relative field length. Assuming the validity of the linear quadratic model of cell survival, the alpha/beta ratio was 1.95 Gy. However, this model fitted the data less well for the least severe levels of damage, and for these the alpha/beta ratios were not significantly different from zero. Irradiation with fast neutrons showed a small effect of fractionation for doses given in greater than or equal to 6 fractions compared with a single dose. There was no significant increase in iso-effect dose when the dose was given in 30 fractions compared with 6 fractions. The relative biological effectiveness for late cutaneous and subcutaneous damage for the energy of fast neutrons used did not vary with the period of assessment, i.e. 26-52 weeks compared with 65-104 weeks, and was not significantly different from that previously obtained for ischaemic dermal necrosis, seen after higher doses, at 12-20 weeks after irradiation.

The dose response relationship obtained at constant irradiation times for the induction of chromosome aberrations in human lymphocytes by cobalt-60 gamma rays.

The induction of unstable chromosome aberrations in human peripheral blood lymphocytes exposed in vitro to protracted doses of cobalt-60 radiation is presented. Four dose response curves have been produced using constant exposure times of 1,3,6, and 12 h. The data fit well to the linear quadratic model and the yield coefficients have been compared with those obtained for acute (less than 10 min) exposure. The quadratic coefficient is dependent on irradiation time and decreases approximately as predicted by Lea and Catcheside's G-function hypothesis. The possibility of a small proportion of much longer lived breaks is discussed. For purposes of biological dosimetry it is sufficient to assume a mean time of 2 h and a single exponential function for the repair of lesions when relating the effects of brief and protracted exposure.

The dose-response for x-ray induction of myeloid leukaemia in male CBA/H mice.

The form of the dose-response for induction of malignant diseases in vivo by ionizing radiation is not yet established in spite of its scientific interest and its practical importance. Considerably extended observations have confirmed that the dose-response for acute myeloid leukaemia induced in male CBA/H mice by X-ray exposure is highly curvilinear. The dose-response was well fitted by the expression aD2e-lambda D (D = dose) in agreement with induction at the cellular level in proportion to D2 over the whole dose range 0.25-6.0 Gy. The factor e-lambda D accounts for the inescapable concomitant inactivating action of the inducing irradiation. The quantitative aspects of induction of myeloid leukaemia by ionizing radiation are unlike the induction of genetic mutation or cell inactivation and suggest that interaction of two adjoining cells is an essential element in radiation leukaemogenesis.

Haemoglobin synthesis by fetal erythroid cells in an adult environment.

Although the developmental switch from fetal to adult haemoglobin production has been well characterized in terms of protein synthesis, very little is known about its control at the cellular level. In order to determine whether the switch is controlled by environmental factors or programmed into the haemopoietic cell population, we have studied the effects of transplantation of fetal and adult haemopoietic cells into lethally irradiated lambs on haemoglobin synthesis by the transplanted cells. In two lambs which were irradiated but not transplanted, two lambs which were grafted with autologous marrow, and one lamb which was grafted from an allogenic twin, haemoglobin synthesis showed an adult pattern following transplantation, with gamma-chain synthesis never exceeding 7% of non-alpha chain production. Of 11 lambs transplanted with fetal haemopoietic cells, only two showed evidence of engraftment. During the 24-26 d that these animals survived, haemoglobin synthesis showed a predominantly fetal pattern, though there was a gradual increase in beta-chain production of donor origin. This increase occurred earlier than would be expected from the gestational age of the transplanted cells, but more slowly than might be expected if environmental factors were entirely responsible for expression of adult or fetal haemoglobin synthesis.

Radiographic features of bone in several strains of laboratory mice and of their tumours induced by bone-seeking radionuclides.

The natural radiographic appearance of the various bones of the skeleton are described for several strains of laboratory mice. The Harwell substrains of CBA, A and 101 are generally similar and become osteoporotic on ageing. Harwell C57BL have similar, but more delicately chiseled, bones. Harwell C3H mice have bones with stouter cortices and may show osteosclerosis on ageing. CF1 females (donated by Dr M. Finkel) showed osteosclerosis and osteophytic outgrowths when aged. NMRI mice (donated by Dr A. Luz) appeared larger than the pure-strain Harwell mice. In general, mouse bones are simple tubular structures with an ivory cortex and a marrow cavity. Cancellous trabecular bone is scanty, even in vertebrae, flat bones and the metaphyses of long bones. Bone-seeking radionuclides administered to mice lead to skeletal tumours: (a) osteosarcomata, which are commonly radio-opaque to a variable degree owing to calcified tumour bone, but which may be osteolytic, (b) primitive mesenchymal (angio-) sarcomata which are non-osteogenic and osteolytic, (c) fibrosarcomata--which also are osteolytic--and to local or general lymphomata from irradiation of parental cells in bone marrow, but no special radiological features have been found associated with these last-named tumours.

The relationship between chromosome aberrations and low LET radiation dose to human lymphocytes.

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.