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R L Maughan

Publications and source records attributed to R L Maughan.

67 records · Page 4Linked to original sources

RBE values for colo-rectal injury after caesium 137 gamma-ray and neutron irradiation. I. Single doses.

Colo-rectal damage in mice has been assessed after caesium gamma irradiation and 3 MeV neutrons given as single doses. Several assays were used, including body weight changes, faecal deformity and lethality. Dose response curves have been constructed for each assay at different times after irradiation, ranging from 10 days to 16 months. The data have been analysed in terms of the time course of expression of damage and the RBE for neutrons. An initial loss of weight at 10-20 days was presumably related to epithelial denudation, but a dose-dependent weight reduction (compared with controls) persisted over the animal's life span. Mice died progressively after localised pelvic gamma irradiation; there was no sharp demarcation between an early and late phase of lethal injury. Death resulted from intestinal stricture or stenosis. The time course for lethality was qualitatively different after neutrons, with little progression of damage between 5 and 11 months. Faecal deformity was detectable as a higher proportion of small pellets when the rectum became constricted by fibrosis. No significant faecal deformity was observed before 6 months after which time dose response curves could be obtained. The RBE for early damage (assessed at 1-3 months) was 2.2-2.7. This fell to 1.7-1.9 for late damage (determined at 10-15 months) over the range of neutron doses of 7.5-12 Gy. The need for sublethal assays allowing for sequential evaluation of radiation damage within the same animal is stressed, as is the need to compare RBE values from early and late endpoints at equivalent neutron doses.

Animals↗

The RBE for mouse skin irradiated with 3-MeV neutrons: single and fractionated doses.

Early skin reactions on the feet of mice were measured after irradiation with 240-kVp X rays or with neutrons from a 4-MV Van de Graaff accelerator. The results are compared with previous experiments using cyclotron-produced neutrons. Single doses, or 2, 5, or 9 equal fractions, were given to measure the RBE and repair capacity for neutrons and X rays over the neutron dose per fraction range from 1.0 to 13.0 Gy. The RBE increased with decreasing dose per fraction, and these data could be fitted with a straight line on a log-log plot. The RBE was 4.6 at 1.0 Gy and fell to 2.1 at 13.0 Gy. These RBE values are significantly higher than those from cyclotron-produced 7.5-MeV neutrons, especially at low doses per fraction. The repair capacity was calculated from a comparison of the single-dose and fractionated data over a skin reaction range from 0.6 to 2.4. The D2 - D1 value was 5-10 Gy for X-ray doses up to 18 Gy and less than 1.5 Gy for 7 Gy of neutrons. This reduced repair capacity after neutrons was even more apparent with further fractionation, becoming close to zero for neutron doses below 3 Gy. These data were used to construct quasi-survival curves for epidermal cells. The X-ray data conform to an alpha D + beta D2 model, whereas the neutron data indicate a predominant alpha component, with the initial response appearing linear from zero to 5.0 Gy. Beyond this dose, however, a potentially reparable beta component of neutron damage is detectable, with the same value of beta as for X rays. Thus it is the greatly increased efficiency of the alpha component relative to X rays, rather than an absence of a shoulder after neutrons, that gives rise to the low D2 - D1 values at low doses and to the high RBE. The ratio of alpha components for X rays and neutrons would indicate a limiting RBE of 7.2 at X-ray doses below 1.0 Gy.

Animals↗

Early and late effects in mouse lung and rectum.

No higher RBE's were found for late than for early damage in mouse rectum up to 70 weeks or mouse lungs up to 48 weeks after irradiation with 3.0 MeV neutrons (4 MeV deuterons on Be). The smallest neutron doses per fraction were 1.5 and 0.6 Gy for rectal and lung irradiation, respectively. There was a suggestion of higher late RBE's for small doses per fraction in the lung. Slow repair after 2 neutron doses split by 31 days was unequivocally demonstrated in the lung, of magnitude about 1 Gy, possibly decreasing after about 40 weeks.

Animals↗

A fast kinetics study of the modes of action of some different radiosensitizers in bacteria.

Using a fast mixing a irradiation technique, the gas explosion method, with Serratia marcescents, the decay of oxygen-dependent damage is found to consist of a fast and a slow stage, each of which is associated with a sub-component of this damage. In the present work, the interactions of these components with radiosensitizers are examined. At low concentrations O2, TAN (a nitroxyl) and misonidazole all preferentially sensitize the slow-stage damage. At higher concentrations, O2 and TAN sensitize the fast-stage damage by a fixation reaction that competes with its repair; in contrast, misonidazole appears mainly to operate by reaction with an earlier, ever shorter form of oxygen-dependent damage.

Kinetics↗

Effects of some hypoxic cell radiosensitizers on the decay of potentially lethal oxygen-dependent damage in fully hydrated spores.

Using a stopped-flow mixing and pulsed irradiation apparatus, a study has been made of the decay, to a harmless form, of radiation-induced species that would otherwise be lethal to spores on contact with oxygen. Aqueous suspensions of Bacillus megaterium spores were irradiated with electrons for approximately 1 s; at various times after irradiation oxygen in solution was added. As the interval between anoxic irradiation and introduction of oxygen increased, the fraction of spores surviving increased. This change in survival reflects the decay of potentially lethal species. The presence of electron-affinic radiosensitizers during irradiation enhanced the decay rate of this damage, the greatest enhancement being seen with sensitizers of the highest electron affinity. In contrast, the nitroxyl-free radical sensitizer TAN fixed the radiation-induced damage so that no increase in survival, and hence no decay, was seen.

Bacillus megaterium↗

The decay of potentially lethal oxygen-dependent damage in fully hydrated Bacillus megaterium spores exposed to pulsed electron irradiation.

Using a stopped-flow mixing and pulsed irradiation apparatus, a study has been made of the decay, to a harmless form, of radiation-induced species which would otherwise be lethal to spores on contact with oxygen. Aqueous suspensions of Bacillus megaterium spores were irradiated with 600 krad of electrons given over approximately 1 s; at various times after irradiation oxygen in solution was added. As the interval between irradiation and introduction of oxygen increased, the fraction of spores surviving increased. For spores irradiated in a deoxygenated condition the decay of the potentially lethal species, reflected by this change in survival, proceeded as if two parallel first-order reactions with half-lives of 9 and 120 s operate. In contrast, for spores equilibrated with oxygen and then irradiated, the decay is described by a single first-order expression with an associated half-life similar to that of the faster of the two reactions operating in anoxia.

Bacillus megaterium↗

Practical aspects of transmission cord blocks in radiotherapy.

We present the advantages of using partial transmission cord blocks throughout treatment, as opposed to adding full-thickness blocks near the end. Such blocks reduce the risk of block omission or mispositioning and require less total time for construction. We also present an argument for the existence of an optimal width for cord blocks used in mediastinal treatments. A figure of merit has been derived which quantifies the tradeoff between narrow blocks, which increase the variation in dose across the block shadow and the risk of positioning errors, and wide blocks, which may unnecessarily shield potential tumor sites. For 60Co, 4- and 10-MV beams, the figure of merit peaks at block widths of 2.0-2.5 cm at the level of the cord. Effective transmission data for cord blocks constructed of cerrobend are given for those three beams. Quality assurance studies show that transmission through cerrobend blocks can be controlled to the required precision.

Cobalt Radioisotopes↗

Influence of tumor site on the therapy of murine kidney cancer.

OBJECTIVE: The purpose of this study was to evaluate the influence of tumor site on the therapy of an experimental murine kidney cancer model, Renca. METHODS: Equal number of tumor cells were injected subcutaneously, intraperitoneally, sub-renal capsule, and intravenously to induce tumors. The animals were then assessed for growth of the primary tumor, metastases and survival. Immunohistochemistry and flow cytometry was performed to identify the phenotype of infiltrating lymphocytes. Tumor bearing animals were treated with high dose interleukin-2 or whole body radiation, and response of the primary tumors as well as the metastases was assessed. RESULTS: Renca tumors grew well regardless of the methods of induction. Spontaneous metastasis could be best induced in the sub-renal capsule model. More consistent numbers of pulmonary metastases were obtained by intravenous injection of the tumor cells. Immunotherapy was able to reduce the size of the primary tumor as well as the number of metastasis. Whole body radiation caused some reduction in the primary tumor but did not have a major effect in reducing metastasis. CONCLUSIONS: The Renca model is a suitable animal model to study the response to different therapeutic interventions. The site of the tumor growth is not a significant variable in the response to treatment.

Adenocarcinoma↗

Radiation therapy enhances the therapeutic effect of immunotherapy on pulmonary metastases in a murine renal adenocarcinoma model.

In order to improve the efficacy of immunotherapy, we have evaluated the effects of radiation therapy combined with interleukin 2 (IL-2) treatment in a murine metastatic renal adenocarcinoma model (Renca). Pulmonary metastases were induced in Balb/c mice by intravenous injection of Renca and five days later a sublethal dose of radiation (300 rads) was administered either to the whole body or to the left lung only. One day following radiation, immunotherapy was given for 5 consecutive days of IL-2 at 5,000 Cetus units intraperitoneally, twice daily. The animals were either sacrificed on day 23 or 33 to assess tumor burden, or were followed for long term survival. We found that pretreatment with irradiation greatly enhanced the therapeutic efficacy of immunotherapy and was manifested by a significant reduction in pulmonary metastases and an increase in survival. When combined with immunotherapy, local tumor irradiation was not only as effective as whole body irradiation, but irradiation of one lung reduced the number of metastases similarly in both lungs. This suggests that local tumor irradiation may act through a systemic mechanism to increase the anti-tumor response mediated by IL-2 therapy.

Animals↗