The effects of fast neutrons on inoperable carcinoma of the stomach.
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Thirty-nine unselected patients suffering from inoperable, recurrent, or residual adenocarcinoma of the stomach were referred for palliation with fast neutrons from the Medical Research Council's cyclotron at Hammersmith Hospital. A full course of 1440 rads given in 12 treatments over 26 days was administered to the patients. Because of the relatively low energy (7-5 MeV) of the beam from this particular machine, it was not possible to deliver the full dose uniformly throughout the tumour except in extremely thin patients. Pain, dysphagia, vomiting, and bleeding were relieved in the majority of cases. The side effects were minimal and easily controlled. Palpable masses disappeared. Five patients required surgery after neutron therapy. All the incisions were made through irradioated tissue and all except one healed normally. Tumour was present outside the treated area, but the absence of any palpable mass within the treated area was a consistent finding. Radiologically, the stomachs remained abnormal and later changes included gross mucosal abnormality and shrinkage. Fourteen patients came to necropsy and in 10 no tumour was present macroscopocally. Tumour cells were seen in all except two cases but these were few, surrounded by dense fibrous tissue, and may not have been viable. The remaining stomach was abnormal with a thickened wall and destruction of mucosa. Three of the four cases in which macroscopic tumour was present received less than the standard dose because of the inadequate penetration of the beam. Excellent regression of tumors was achieved by the neutrons, but the stomachs did not recover from this satisfactorily. Gastrectomy four to six months after treatment is therefore suggested. This operation and other surgical procedures in other patients were successfully carried out. There is a need for higher energy neutrons to improve treatment and extend it to patients of thick-set build. (+info)
In vivo measurement of body nitrogen by analysis of prompt gammas from neutron capture.
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A method for the in vivo determination of body nitrogen by prompt gamma photons from neutron capture is described. An 85-Ci 238Pu-Be source provides the neutrons. The gamma detection system consists of two 15.24 x 15.24 cm Nal(TI) detectors placed above the patient. Absolute value of body nitrogen is determined using body hydrogen as an internal standard. The reproducibility of the method is +/- 3% for a body dose of 26 mrem. (+info)
The survival of parenchymal hepatocytes irradiated with low and high LET radiation.
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We have developed an in vivo clonogenic assay system for parenchymal hepatocytes which has enabled us to investigate the reproductive survival and repair capacity of liver cells exposed to genotoxic agents. In this report we present our results with hepatocytes irradiated 60Co and neutrons. The survival curve for parenchymal hepatocytes enzymatically dispersed 30 min after exposure to 60Co has a D0 value of 2.7 Gy and an extrapolation number insignificantly different from unity. However, when the hepatocytes were allowed to remain in situ for 24 h before being assayed for survival, the extrapolation number significantly increased to 2.3, whereas the D0 value remained unchanged. Therefore, normal parenchymal hepatocytes in G0 are able to repair potentially lethal damage (PLD) after exposure to 60Co and this repair phenomenon is expressed solely as an increase in the n value. In contrast, with hepatocytes exposed to 14.3 MeV neutrons, the survival curve is exponential with a D0 value of 1.7 Gy regardless of whether the cells remained in situ for 30 min or 24 h before the assessment of their reproductive survival. A comparison of the 60Co and neutron survival curves, where 24 h is allowed for PLD repair to occur, demonstrates that the RBE of neutrons for hepatocytes increases with decreasing dose and equals 4.2 at 50 cGy. The radioprotective agent WR-2721 was shown to act as a dose modifying agent with a DMF of 2.1, implying that it may be of potential clinical value as a radiation hepato-protective drug. (+info)
Fast neutron treatment as an alternative to radical surgery for malignant tumours of the facial area.
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Thirty one patients with very advanced tumours of the maxillary sinus were treated with fast neutrons. Tumour regressed completely in 29 (94%) and subsequently recurred in four (14%). No surgical excision of bone, skin, or nerve was required, and an artificial eye was well tolerated in cases where the eye received the tumour dose and had to be removed. Complications occurred in 10 patients, two of whom had already received radical x ray treatment. The overall duration of neutron treatment was four weeks, and admission to hospital was usually unnecessary. These results compared well with those obtained with surgery. Surgery with curative intent for even moderately advanced tumours of the facial region, particularly the paranasal sinuses, results in deformity, which is often severe and always irreversible. Even so, the cure rate is only about 35%. The high rates of tumour control and the avoidance of severe cosmetic and functional defects after fast neutron treatment make it an alternative to radical surgery in the management of malignant tumours of the facial area. (+info)
Differences in repair in heterogeneous cell populations in vivo and in vitro following high LET irradiation (neutrons).
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The shape of cell survival curves following X-irradiation when the X-rays were given immediately after neutron irradiation has been examined in two cell lines in vitro (Ehrlich ascites and V79) and in the stem cells of the mouse jejunum. The changes in the shape of the X-ray survival curve following neutron irradiation are different in all the cell systems examined. Some of the changes observed may be associated with a change in the cell profile following neutron irradiation due to the more even cell age killing pattern of neutrons through the cell cycle compared with X-rays. It is unlikely that this can account for all changes in shape observed and it is postulated that some cells following neutron irradiation are more sensitive to X-rays than the unirradiated population or than X-irradiated cells at the same level of survival. This increased sensitivity may be associated with a non-reversible sublethal damage or a saturation of the repair potential caused largely by the alpha or heavy recoil (HR) particles produced by the neutrons in the cell nucleus. The damage is observed when the probability of alpha or HR particles being produced within the cell nucleus, without killing the cell, is high. (+info)
Possible error-prone repair of neoplastic transformation induced by fission-spectrum neutrons.
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We have examined the effect of fission-spectrum neutrons from the JANUS reactor at Argonne National Laboratory, delivered either as acute or protracted irradiation, on the incidence of neoplastic transformation in the C3H 10T1/2 mouse embryo cell line. Acute exposures were delivered at 10-38 cGy min-1, protracted exposures at 0.086 or 0.43 cGy min-1. The total doses for both ranged from 2.4 to 350 cGy. In the low dose region (2.4-80 cGy), there was a large enhancement in transformation frequency when the neutrons were delivered at the low dose rates compared with the high dose rates, but the survival of the cells was not significantly different between the two exposures conditions. Analysis of the initial parts of the curves shows that the regression line for protracted doses is about 9 times steeper than that for single acute exposures. Finally, the possibility is discussed that an "error-prone" repair process may be causing the enhanced transformation frequency by protracted neutron exposures. (+info)
Enhanced transformation of mouse 10T1/2 cells by 12-O-tetradecanoylphorbol-13-acetate following exposure to X-rays or to fission-spectrum neutrons.
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Addition of the tumor promoter of 12-O-tetradecanoylphorbol-13-acetate (TPA) to C3H/10T1/2 cells after exposure to either X-rays or to fission-spectrum neutrons increases significantly the frequency of transformation without any effect on cell survival. However, treatment of unirradiated cells with 0.1 micrograms of TPA per ml alone results in a small increase in transformation frequency above background (i.e., from 1.1 x 10(-5) to 1.0 x 10(-4). Thus, besides being a promoter, TPA is also a weak initiator. Enhancement of radiation-induced transformation by TPA was relatively greater after low compared to high doses of either radiation. In addition, TPA causes the relative biological effectiveness of neutrons compared to X-rays to increase with increasing dose or with increasing frequency of transformation rather than to decrease, when TPA is not used. For X-ray doses from zero to approximately 120 rads, TPA raises transformation to frequencies approximately equal to those due to neutrons alone. Analysis of TPA enhancement in the context of the combined effect of two inducing agents, i.e., TPA plus a radiation, indicates that with either radiation TPA acts synergistically. Lastly, TPA was found to alter the dependence of transformation frequency on the density of viable cells. As opposed to a constant frequency of transformants per surviving (or viable) cell, which we observed after a fixed dose of X-rays or neutrons for a range of cell inocula, the addition of TPA increased the frequency of transformation for cell inocula (i.e., from approximately 20 to 6000 viable cells per 90-mm Petri dish). However, the frequency of transformation decreases with increasing size of the inoculum, a result that we interpret to indicate the combined effect of an interference with cell-to-cell communication by TPA plus the fading of initiation events due to the radiation. (+info)
Self-incompatibility system of Oenothera organensis for the detection of genetic effects at low radiation doses.
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The self-incompatibility system of Oenothera organensis is used to analyze the frequency of S locus mutations induced by low doses (2.5-20 rad) of fast neutrons and x-rays. Th principles and methods of the screening system for detection of low dose effects have been presented. The results show that low doses induced significantly higher frequencies of seeds and seedlings than those produced spontaneously. The analyses of part of the progenies derived from the control and treated series suggested that they were due to revertible mutations. A modified in vitro method of culturing pollinated cut styles has been developed for rapid screening of compatible pollen tubes. (+info)