International journal of radiation biology and related studies in physics, chemistry, and medicine最新文献

A/Jax (A/J) mice primed to Sarcoma I (SaI) exhibit an augmented response in association with low-dose (0.15 Gy) irradiation. This phenomenon is best demonstrated in tumour neutralization (Winn assay) or cell transfer experiments utilizing mice depleted of thymus-derived (T) cells. It is particularly dependent upon the duration of priming and the growth characteristics of the tumour in the primary host. The importance of these two variables appears to relate to their influence upon the cell types responsible for the host response, and includes both an effector and a suppressor component. Radiation-induced inhibition of the suppressor component appears responsible for low-dose augmentation and results in injury to a T cell of the Lyt-1-2+ phenotype. In Winn assays employing equal numbers of immune spleen cells and SaI cells, the smallest tumours are associated with Lyt-1-positive (Lyt-1+2- and Lyt-1+2+) cells and exposure to 0.15 Gy markedly inhibits their anti-SaI activity. Thus, even though the effect is in the opposite direction, both the effector and suppressor components of the anti-SaI response in A/J mice are exceedingly radiosensitive.

Studies on the immediate and long-term effects of radiation on the immune system of specific-pathogen-free mice are summarized in this paper. There was a striking difference in the radiation response of lymphocyte subsets; B cells consist of a fairly radiosensitive homogeneous population, whereas T cells consist of a large percentage (greater than 90 per cent) of radiosensitive and a small percentage (less than 10 per cent) of extremely radioresistant subpopulations. Ly 1+ and Ly 2+ lymphocytes appear equally radiosensitive, although the percentage of radioresistant cells was slightly larger for the former (approximately 5.5 per cent) than the latter (approximately 2.5 per cent). There was a significant strain difference in the radiosensitivity of immune-response potential in mice; immunocompetent cells of C3H mice were more radioresistant than those of BALB/c, C57BL/6, and B10.BR mice. Studies on the long-term effect of radiation on immune system in mice indicated no evidence for accelerated ageing of the immunologic functions when radiation exposure was given to young adults. Preliminary results on the enhancing effect of low dose radiation on cytotoxic T cell response in vitro are also discussed.

Low-dose irradiation is usually considered to be rather ineffective in producing biologically relevant effects. Yet, individual radiation absorption events within cell nuclei or whole cells interact stochastically with subcellular structures due to the multiple ionizations along primary or secondary particle tracks, depending on ionization density. Whereas radiation effects are usually seen in the context of structure and function of DNA, other cellular effects, perhaps influencing DNA by secondary biochemical mechanisms, also warrant attention. Thus, previous work from this laboratory with bone marrow that was obtained from whole-body exposed mice, has shown that single or few instantaneous radiation absorption events per cell from gamma-rays produce an acute and temporary partial inhibition of the enzyme thymidine kinase; the effect appears within about 1 h after the event, reaches its maximum at approximately 4 h and disappears completely within another 6 h. This pattern of enzyme inhibition is fully concordant with the pattern of inhibition of uptake of tritiated thymidine or 125I-labelled deoxyuridine into the DNA; also concordant is a temporary increase in the concentration of free thymidine in the blood serum of the exposed mice. The particular response of thymidine kinase was considered to relate to some, thus far unknown, repair systems and/or to a defence mechanism of the hit cells. In order to further elucidate the role of the acute and temporary partial inhibition of thymidine kinase in cellular metabolism, experiments were carried out in which mice were acutely exposed to 0.01 or 0.1 Gy and again exposed to the same dose at different times up to 12 h after the first exposure. At regular time intervals after the second exposure bone marrow cells were obtained and thymidine kinase activity was studied by various assays. The results indicate that the first acute irradiation conditioned the cells in such a way that the second acute irradiation produced either an enhanced inhibition and recovery of thymidine kinase activity, or no effect at all was seen, when the second irradiation was given between about 3 and 8 h after the first irradiation. From 8 to 12 h after the first irradiation the cells apparently resumed their original state, so that the second irradiation produced effects quite similar to those seen after a single irradiation in unconditioned cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Oxygen (O2) sensitizes bacterial cells in at least two mechanistically different ways, depending on the specific O2 concentration present during irradiation. Based on previous work from this laboratory, it has been proposed that nitrous oxide (N2O) and low concentrations of O2 share a common mechanism for damage. This mechanism, involving the production of superoxide anion radicals (O2-), is different from that which causes damage at high O2 concentrations. Others, however, have presented evidence that N2O and O2 (usually tested only at high concentrations) act in different ways to sensitize bacterial cells. We have now measured the radiation sensitivity in mixtures of N2O and O2 to observe additivity patterns and to determine if these two agents have any common processes for sensitization. We found that some low O2 concentrations do not increase the response in N2O, although they can have significant sensitizing effects in N2. This lack of additivity is taken as evidence for a common mechanism of damage from N2O and low concentrations of O2. In contrast, damage from high concentrations of O2 is additive to the damage from N2O. The greatest sensitivity, observed with a gas mixture of about 15 per cent O2/85 per cent N2O, is equivalent to the response in 100 per cent N2 plus the maximum amount of damage O2 can cause plus the maximum amount of damage N2O can cause. This additivity is taken as evidence that N2O and high concentrations of O2 sensitize in different ways. Thus, O2 is known to sensitize these bacteria in at least two different ways; one of these is apparently also the way N2O sensitizes.

Using the neutral filter elution technique, the induction of DNA double-strand breaks (dsb) has been measured in 250 kVp X-irradiated V79-379A Chinese hamster cells irradiated under air or nitrogen. The dose-effect curves for induced dsb were curvilinear, mirroring cell survival curves, such that there was an approximately linear relationship between induced dsb and lethal lesions (-In (cell survival)) which was independent of oxygen. With cells irradiated with 2.3 MeV neutrons or 238Pu alpha-particles the correlations between lethal events and dsb, although also approximately linear, do not match those for X-rays. With neutrons there is approximately a 2.5-fold reduction in the level of dsb induction per lethal event. Thus either the apparently linear relationships found are spurious, and there is no general correlation between induced dsb and lethal effect, or there are qualitative differences between neutron, alpha-particle and X-ray induced dsb that give them differing probabilities of cell kill.

The effect of thermal neutrons on the induction of murine endogenous viruses from a mouse fibroblast cell line was investigated. Thermal neutrons were more effective than X-rays in induction of endogenous virus as well as in killing of the cells. However, when measured as a function of cell killing, both radiations had similar efficiency of induction. The RBEs of thermal neutrons alone were calculated on the assumption that the contribution of contaminating gamma-rays was additive. It was 4.2 for the killing effect and 4-5 for virus induction.

The findings of Hill et al. (1984) on the greatly enhanced transformation frequencies at very low dose rates of fission neutrons induced us to perform an analogous study with alpha-particles at comparable dose rates. Transformation frequencies were determined with gamma-rays at high dose rate (0.5 Gy/min), and with alpha-particles at high (0.2 Gy/min) and at low dose rates (0.83-2.5 mGy/min) in the C3H 10T1/2 cell system. alpha-particles were substantially more effective than gamma-rays, both for cell inactivation and for neoplastic transformation at high and low dose rates. The relative biological effectiveness (RBE) for cell inactivation and for neoplastic transformation was of similar magnitude, and ranged from about 3 at an alpha-particle dose of 2 Gy to values of the order of 10 at 0.25 Gy. In contrast to the experiments of Hill et al. (1984) with fission neutrons, no increased transformation frequencies were observed when the alpha-particle dose was protracted over several hours.

Considerable interest has been aroused in recent years by reports that the transforming and carcinogenic effectiveness of low doses of high LET radiations can be increased by reducing the dose rate, especially for transformation of 10T1/2 cells in vitro by fission-spectrum neutrons. We report on conditions which have been established for irradiation of 10T1/2 cells with high LET monoenergetic alpha-particles (energy of 3.2 MeV, LET of 124 keV microns-1) from 238Pu. The alpha-particle irradiator allows convenient irradiation of multiple dishes of cells at selectable high or low dose rates and temperatures. The survival curves of irradiated cells showed that the mean lethal dose of alpha-particles was 0.6 Gy and corresponded to an RBE, at high dose rates, of 7.9 at 80 per cent survival and 4.6 at 5 per cent survival, relative to 60Co gamma-rays. The mean areas of the 10T1/2 nuclei, perpendicular to the incident alpha-particles, was measured as 201 microns2, from which it follows that, on average, only one in six of the alpha-particle traversals through a cell nucleus is lethal. Under the well-characterized conditions of these experiments the event frequency of alpha-particle traversals through cell nuclei is 9.8 Gy-1.

Whole-body hyperthermia (WBH) to 41-42 degrees C combined with fractionated total-body irradiation (TBI) was studied in mice with transplanted AKR leukemia. Mice treated with both TBI and WBH survived longer than mice treated with either modality alone. From other groups of similarly treated mice the spleens were removed, weighed, and assayed for their content of leukemic colony-forming units (CFU) by injecting single-cell suspensions into normal syngeneic recipients. Using this methodology it was determined that the thermal enhancement ratio for WBH combined with TBI was 1.6, and that enhanced killing of leukemia cells occurred irrespective of the sequence of WBH and TBI. Data are presented which relate variables, such as duration of WBH or heating time to target temperature, to the response of neoplastic disease. The implications of these preclinical findings to clinical trials are discussed.