The Journal of pharmacy and pharmacology
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J. Pharm. Pharmacol. · Aug 2008
ReviewMechanism of radiation-induced bystander effects: a unifying model.
The radiation-induced bystander effect represents a paradigm shift in our understanding of the radiobiological effects of ionizing radiation, in that extranuclear and extracellular events may also contribute to the final biological consequences of exposure to low doses of radiation. Although radiation-induced bystander effects have been well documented in a variety of biological systems, the mechanism is not known. It is likely that multiple pathways are involved in the bystander phenomenon, and different cell types respond differently to bystander signalling. ⋯ Inhibitors of nitric oxide (NO) synthase (NOS) and mitochondrial calcium uptake provided evidence that NO and calcium signalling are part of the signalling cascade. The bystander observations imply that the relevant target for various radiobiological endpoints is larger than an individual cell. A better understanding of the cellular and molecular mechanisms of the bystander phenomenon, together with evidence of their occurrence in-vivo, will allow us to formulate a more accurate model for assessing the health effects of low doses of ionizing radiation.
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J. Pharm. Pharmacol. · Aug 2008
ReviewAmelioration of the pathological changes induced by radiotherapy in normal tissues.
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. ⋯ 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.