[en] The apoptotic response induced by radiation is discussed, with particular emphasis on its control in relation to radiotherapy. Topics discussed are: - the apoptotic response and the absence of inflammation, control of apoptosis, initiating stimulus-lag-apoptotic response, the MADCaT approach in cancer treatment strategies, and selective susceptibility and hypersensitivity of cells to radiation-induced apoptosis. (UK)

[en] This paper presents a summary of the morphological categorization of cell death, results of two in vivo studies on the cell death induced by mild hyperthermia in rat small intestine and mouse mastocytoma, and a comparison of the cell death induced by hyperthermia, radiation and cytotoxic drugs. Two distinct forms of cell death, apoptosis and necrosis, can be recognized on morphologic grounds. Apoptosis appears to be a process of active cellular self-destruction to which a biologically meaningful role can usually be attributed, whereas necrosis is a passive degenerative phenomenon that results from irreversible cellular injury. Light and transmission electron microscopic studies showed that lower body hyperthermia (43 degrees C for 30 min) induced only apoptosis of intestinal epithelial cells, and of lymphocytes, plasma cells, and eosinophils. In the mastocytoma, hyperthermia (43 degrees C for 15 min) produced widespread tumor necrosis and also enhanced apoptosis of tumor cells. Ionizing radiation and cytotoxic drugs are also known to induce apoptosis in a variety of tissues. It is attractive to speculate that DNA damage by each agent is the common event which triggers the same process of active cellular self-destruction that characteristically effects selective cell deletion in normal tissue homeostasis

[en] The cells of the external granular layer (EGL) of the developing cerebellum are known to be particularly sensitive to radiation. In the past, changes induced in this layer by irradiation have been referred to by non-specific terms such as pyknotic cells and the mode of cell death has been assumed to be necrosis. However, in published light micrographs of these dying cells, the appearance is suggestive of apoptosis, a distinctive mode of cell death which occurs spontaneously in normal adult and embryonic tissues and can also be triggered by certain pathological stimuli. This light and transmission electron microscopic study of control and irradiated (7 h post-irradiation) rat cerebellum from 18 day fetuses and 5 day-old neonates showed that the cell death was effected by apoptosis. The apoptosis was markedly enhanced by x-irradiation and quantification of the cell death in the EGL of 5 day-old rats exposed to 4, 8, 25, 100, and 400 cGy x-irradiation demonstrated that there was a positive dose response relationship. The extent of cell death by apoptosis which was 0.2% in control, ranged from 0.8% after 4 cGy to 62.3% after 400 cGy x-irradiation. The recognition that cell death by apoptosis can be a major component of x-irradiation damage has important implications for radiobiological studies

[en] The importance of the morphological study of cell death has recently been emphasized by the recognition that the ultrastructural features of dying cells allow categorization of the death as either apoptosis or necrosis. This classification enables inferences to be drawn about the mechanism and biological significance of the death occurring in a particular set of circumstances. In this study, Sertoli cell death induced in the immature testis of three and four day old rats by 5 Gy (500 rads) x-irradiation was described by light and transmission electron microscopy with the objective of categorizing the death as apoptosis or necrosis. The testes were examined 1, 2, 3, 4, 8, and 24 h after irradiation. Following irradiation, there was a wave of apoptosis of the Sertoli cells starting in three to four hours and reaching a peak between four and eight hours. At 24 hours, only 61% of the expected number of Sertoli cells remained. These findings are in accord with recent ultrastructural reports that ionizing radiation induces cell death by apoptosis in rapidly proliferating cell populations. New insights into the pathogenesis of radiation-induced cell death might thus be expected to stem from future elucidation of the general molecular events involved in triggering apoptosis

[en] Short communication. 2 refs

[en] Abstract only

[en] The difference in incidence of radiation-induced apoptosis between two neonatal urogenital tissues, kidney and testis, was analysed over a 24h period. Concurrent administration of cycloheximide (10mg/kg body weight), a protein synthesis inhibitor, with radiation treatment was used to determine whether new protein synthesis had a role in induction of apoptosis in this in vivo model. Many chemotherapeutic drugs act via protein synthesis inhibition, and we believe that the results of this latter analysis may provide information for the planning of concurrent radio and chemotherapy. Apoptosis was quantified using morphological parameters, and verified by DNA gel electrophoresis for the typical banding pattern, and by electron microscopy. The proliferative index in tissues was studied, using [6-³H]-thymidine uptake ( 1h prior to euthanasia and collection of tissues) and autoradiography as indicators of cell proliferation (S-phase). Tissue was collected 2, 4, 6, 8, and 24h after radiation treatment. Expression of one of the apoptosis-associated genes, Bcl-2 (an apoptosis inhibitor/cell survival gene), was studied using immunohistochemistry. Apoptosis peaked at 4h in the testis and 6h in the kidney, emphasising the necessity of knowing tissue differences in radiation response if comparing changes at a particular time. A higher proportion (almost five fold) of the apoptotic cells died in S-phase in the kidney than the testis, over the 24h. Protein synthesis inhibition completely negated induction of apoptosis in both tissues. Necrosis was not identified at any time. Cycloheximide treatment greatly diminished Bcl-2 expression. The differences in response of the two tissues to irradiation relates to their innate cell (genetic) controls, which may be determined by their state of differentiation at time of treatment, or the tissue type. This in vivo study also suggests the model may be useful for analysis of other cancer therapies for example polychemotherapies or chemo-and radiotherapy

[en] Short communication. 2 refs

[en] Short communication. 3 refs

[en] The induction of extensive apoptosis by tracer doses of ³²P has the potential to invalidate the results of biochemical studies using this and possibly other radioactive isotopes. (author)