The effects of single and fractionated doses of X-rays and neutrons on the oesophagus.
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Biomedical subjects
Publications and source records attributed to S Hornsey.
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The effects of both hyperthermia alone and X-rays combined with hyperthermia on mouse testis have been investigated. Testis weight on heating time was observed for temperatures in the range 39.5 to 43.75 degrees C. The relationship between the reaction rate and the reciprocal of absolute temperature indicated that, over the temperature range considered, the activation energy associated with such thermal damage was (646 +/- 45) x 10(3) J mol-1. No evidence was obtained to indicate a change in slope of the Arrhenius plot over this temperature range. Finally, despite the high sensitivity of the testis to heat and X-rays, no thermal enhancement of the weight loss after irradiation was observed when thermal treatments which, if given alone would produce some observable damage, were administered immediately after irradiation.
The skin reactions in aerated and hypoxic mouse tails after single or fractionated doses of 250 kV X-rays or fast neutrons (6 MeV deuterons on beryllium) have been measured. The o.e.r. for one to sixteen fractions of X-rays remains constant, while that for one to ten fractions of neutrons decreases with increasing neutron fractionation and decreasing neutron dose/fraction. The o.e.r. for X-rays was 1.7, for single-neutron doses 1.4, and for ten fractions of neutrons 1.25. It was anticipated that the o.e.r. for neutron-induced damage would decrease further as neutron fractionation is increased because the contribution to damage from the highest LET components of dose, the alpha and heavy recoil particles, would increase relative to the lowe LET components. The r.b.e. values obtained for skin damage were higher at all neutron doses/fraction examined in this study on tails than all those previously obtained in studies on skin at other sites on four species. This may be due to the influence of hypoxia on the r.b.e. measurements in the mouse tail.
The effects of X-rays and neutrons on human lymphocytes in vitro has been tested. Radiation sensitivity of untransformed lymphocytes was assessed by the appearance of pyknotic cells, and the response of cells after stimulation by phyto-haemagglutinin was tested (a) morphologically and (b) by changes in DNA synthesis, using a labelled thymidine analogue. The data obtained for interphase cells suggest that lymphocytes are a mixed cell population with an insensitive component forming about 20 per cent of the population. The percentage of normal cells observed after both X-ray and neutron irradiation lie on the same dose--effect curve giving an r.b.e. of one. A biphasic response is seen after PHA stimulation with both tests of damage indicating at least two sub-populations of lymphocytes and these give r.b.e. values in the range 1.95 to 2.45. Providing the in vivo response is similar to that in vitro the r.b.e. for damage to circulating lymphocytes will be small and the reduction in white cell count will not therefore be a major factor limiting dose in neutron therapy.
The tolerance of the rat lumbar spinal cord to single and multiple doses of X irradiation has been studied using paralysis of the hind legs as the endpoint. The paralysis, which has an acute onset progressing from the first symptoms to full paralysis within two to three days, occurs within one year post-irradiation. Dose/effect relationships were estimated at one year. Experiments which were designed to study the effect of varying the overall treatment time between two equal doses of X rays showed that a large amount of recovery from irradiation damage occurred during the first 24 hours after irradiation (D2-D1 at 24 hours was 950 rad). No further recovery took place for another 15 days but at 32 days another wave of recovery seemed to be in progress (D2-D1 at 32 days was 1250 rad). The effect of varying the number of fractions independently of the overall treatment time was investigated. The tolerance of the cord increased rapidly as the number of fractions given in a six-week period was increased from four to 30. The slope of a Strandqvist-type plot of this data was about 0.4. The data for the spinal cord have been compared with similar data for late damage in the mouse lung. The latent period between irradiation and the onset of paralysis was also investigated. At high doses, when the probability of paralysis occurring was great, the latent period was independent of the dose. At lower doses which gave rise to a lower incidence of paralysis, the latent period was inversely related to the dose. A second type of paralysis occurred later than one year after irradiation. This had a very protracted development and occurred in unirradiated as well as irradiated animals.
The response of melanomas was assessed retrospectively from the clinical notes on 52 patients from three centres in the United Kingdom. The response was very variable. A tentative isoeffect curve was fitted to the UK data which gave a good fit to data from a prospective study from Yale. Clinical data from the Melbourne Clinic on response and fraction size showed a similar response to that from the UK and the combined data showed that the response to fraction sizes of 400-800 rad was significantly better (p about 0.01) than to fraction sizes of 200-299 rad.
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The relative biological effectiveness (RBE) for damage to mouse lung was measured for single doses and up to 30 fractions of 8 MV x rays and fast neutrons, relative to 250 kVp x rays. With 8 MV x rays the RBE was 0.87 and did not vary with dose per fraction between 150 and 1200 rad. With fast neutrons the RBE did not vary from 1.5 at 1200 rad of x rays, which is about 30% lower than that for skin, to 3.7 at 150 rad of x rays, which is about 10% less than that for skin. The implications for treatment of the lung with fast neutrons are discussed.