Tissue and molecular response to the ionizing radiation (original) (raw)
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Amelioration of the pathological changes induced by radiotherapy in normal tissues
Journal of Pharmacy and Pharmacology, 2008
Damage to normal tissues remains the most important limiting factor in the treatment of cancer by radiotherapy. In order to deliver a radiation dose sufficient to eradicate a localised tumour, the normal tissues need to be protected. A number of pharmacological agents have been used experimentally, and some clinically, to alleviate radiation damage to normal tissues but at present there is no effective clinical treatment to protect normal tissues against radiation injury. This paper reviews the efficacy of pharmacological substances used after radiation exposure. The limited evidence available suggests that radiation insult, like many other tissue injuries, is amenable to pharmacological intervention. However, care must be taken in the administration of these substances for the management of different aspects of radiation damage because there appears to be a tissue-specific response to different pharmacological agents. Also, one must be aware of the limitations of results obtained from animal models, which do not necessarily correlate to benefits in the clinic; the conflicting results reported with some modifiers of radiation damage; and the toxicity of these substances and radiation doses used in published studies. Conflicting results may arise from differences in the pathophysiologic processes involved in the development of radiation lesions in different tissues, and in the markers used to assess the efficacy of treatment agents.
Radiobiological Research For Improving Tumor Radiotherapy -An Indian Perspective*
Radiation-induced damage to normal tissues within the non-target volume is a major limitation of tumor radiotherapy. Physical methods to obtain superior spatial dose distributions use sophisticated technology and are expensive. Large scale applications of these technologies in a developing country like India; with a large number of cancer patients, poor' instrumental facilities and inadequate infrastructure face several problems. Radiobiological research aiming at developing simple, inexpensive and effective methods to increase the differential response between tumor and normal tissues should be, therefore, strengthened.
Radiobiological Research for Improving Tumour Radiotherapy An Indian Perspective
Defence Science Journal, 1990
Radiation-induced damage to normal tissues within the non-target volume is a major limitation of tumor radiotherapy. Physical methods to obtain superior spatial dose distributions use sophisticated technology and are expensive. Large scale applications of these technologies in a developing country like India; with a large number of cancer patients, poor' instrumental facilities and inadequate infrastructure face several problems. Radiobiological research aiming at developing simple, inexpensive and effective methods to increase the differential response between tumor and normal tissues should be, therefore, strengthened. Biological end-points are determined not only by the molecular lesions produced due to the absorption of the radiation energy but also by the cellular repair processes, which become operative in response to lesions in the living system. Therefore, enhancement of repair processes in the normal tissues and inhibition of the same in tumors should considerably improve the therapeutic index of radiation treatment. A combination of agents which can su$abIy alter the spectrum of important molecular lesions with modifiers of cellular repair could be an effective strategy. Initial ezperiments using halopyrimidines to increase repairable DNA lesions produced by sparsely ionizing radiations in combination with 2-deoxy-D-glucose to modulate differentially the repair and fixation processes in the tumor and normal tissues have provided promising results. Further research work is warranted since this strategy appears to have great potential for improving tumor radiotherapy.
Studies on the radiobiology of a rat sarcoma treated in situ and assayed in vitro
European Journal of Cancer (1965), 1973
Some of the characteristics of a rat sarcoma, induced by subcutaneous implantation of a plastic film, have been described. Cells from this tumour can be plated routinely into dishes with a plating efficiency of about 2ยท6% and survival can be assayed by a direct in in vitro cloning technique. The cultured cells, when reinjected intradermally in rats, give rise to solid tumours similar in appearance and histology to the tumour of origin.Irradiation experiments have been performed by treating the tumour cells either in situ or in vitro and by assaying the survival either in vivo or in vitro. The results indicated that the survival of tumour cells irradiated in situ was greater than that of cells irradiated in vitro independently from the assay being done either in vivo or in vitro. This difference could not be accounted for even if it was assumed the cells in situ were completely anoxic.Further experiments demonstrated that the cells in situ are normally sensitive to the synchronizing (lethal and blocking) action of hydroxyurea and that hydroxyurea-synchronized populations exhibited an X-ray age-response similar to that of other systems in terms of the course of the survival variations during the cell cycle (but not in terms of radiation dose).
The Radiobiology of Conventional Radiotherapy and Its Application to Radionuclide Therapy
Cancer Biotherapy and Radiopharmaceuticals, 2005
The linear-quadratic (LQ) model of radiobiological effect is well established in conventional, i.e., external beam, radiotherapy. Because the model is derived from sound biophysical principles, it is also emerging as the standard formalism for assessing biological responses for the whole range of radiotherapy treatments. A central feature of LQ methodology is the quantity known as the biologically effective dose (BED), which may be used to quantify the radiobiological impact of a treatment on both tumors and normal tissues. The BEDs commonly associated with conventional therapy may thus be compared to those expected from novel radiotherapy treatments, such as targeted radionuclide therapy. This approach also provides a mechanism for designing targeted treatments which are therapeutically equivalent to external beam treatments. In this paper the LQ methodology is outlined and worked examples are provided which demonstrate the tentative link between targeted radiotherapy doses and those used in conventional radiotherapy. The incorporation of an allowance for relative biological effectiveness (RBE) effects is also discussed. The complexity of the subject and the potentially large number of variables does place a restriction on overall predictive accuracy and the necessary caveats are outlined.
Radioprotectors of Normal Tissues and Radiosensitizers of Malignant Cells
2004
The in vitro effect of O-LM on radiosensitivity of different human cell lines and the in vivo tolerance to high doses of ionizing radiation induced by the combination of Se, Zn and Mn plus Lachesis muta (O-LM) was evaluated. Sprague-Dawley rats received whole-body irradiation with a single dose (2 to 15 Gy) employing a Cs source of 189 TBq (7.7 Gy/min). A half of rats received daily sc O-LM starting 10 days before irradiation. These animals receiving 8, 10, and 12 Gy showed significantly higher survival versus controls (p<0.0001, 0.003 and 0.0083, respectively). LD50 value for O-LM treated rats was 9.6 Gy vs. 5.8 Gy for controls (p<0.0001). The protective effect of O-LM was also in vivo evaluated on small intestine and bone marrow of nude mice irradiated with a single whole-body dose of 10 Gy. Mice were sacrificed 5 days after irradiation. Mice receiving sc daily O-LM starting 90 days before irradiation, showed better villous and crypts conservation, lack of oedema and vascula...
Genes, 2012
Although radiation carcinogenesis has been shown both experimentally and epidemiologically, the use of ionizing radiation is also one of the major modalities in cancer treatment. Various known cellular and molecular events are involved in carcinogenesis. Apart from the known phenomena, there could be implications for carcinogenesis and cancer prevention due to other biological processes such as the bystander effect, the abscopal effect, intrinsic radiosensitivity and radioadaptation. Bystander effects have consequences for mutation initiated cancer paradigms of radiation carcinogenesis, which provide the mechanistic justification for low-dose risk estimates. The abscopal effect is potentially important for tumor control and is mediated through cytokines and/or the immune system (mainly cell-mediated immunity). It results from loss of growth and stimulatory and/or immunosuppressive factors from the tumor. Intrinsic radiosensitivity is a feature of some cancer prone chromosomal breaka...