**1. Introduction**

482 Selected Topics in DNA Repair

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Radiation has been considered an enigma to the general public and the use of radiation for therapeutic and other uses has always been associated with some skepticism. Presently, ionizing radiation is being used in a large number of therapeutic, industrial and other applications apart from for the generation of nuclear power, developing new varieties of high-yielding crops and enhancing storage period of food materials. Radiation treatment is an important therapeutic option for a number of malignancies, but its use is frequently limited due to adverse effects on normal tissues because it generates reactive oxygen species (ROS) such as hydroxyl radical (·OH), superoxide radicals (O2-.), singlet oxygen and peroxyl radicals (ROO. ) in irradiated tissue that induce several pathophysiological changes in the body. The goal of most cancer treatments is to maximize the antineoplastic effect while minimizing harmful side effects for the patient.

Due to the increased use of ionizing radiation in various aspects of human life, there is a need to develop an effective and non-toxic radioprotector. Radioprotectors are compounds that are designed to reduce the damage in normal tissues caused by radiation. These compounds are often antioxidants and must be present before or at the time of radiation for their effectiveness. Other agents, termed mitigators, may be used to minimize toxicity even after radiation has been delivered. Many natural and synthetic chemicals have been investigated in the recent past for their efficacy to protect against radiation-induced damage in biological systems (Maurya et al. 2006). Though a large number of compounds have been shown to be promising as radioprotectors in laboratory studies, few could pass the transition from bench to bedside. In fact, no radioprotective agent is now available, either alone or in combination to meet all the requisites of an ideal radioprotector. Amifostine is the only one that is currently in use having good radioprotection, even though there are reports about contraindications in some cases. Different radioprotectors offer protection to cellular molecules by different mechanisms (Maurya et al. 2006). Some of these compounds protect the target molecules because of their antioxidant mechanism by neutralizing the free radical, some enhances the cellular DNA repair (Maurya et al. 2005a; Maurya et al. 2005b), some modified the signaling pathways, some modulate the immune system and some contribute to a combination of all above mentioned mechanisms.

Role of Radioprotectors in the Inhibition of DNA Damage

and Modulation of DNA Repair After Exposure to Gamma-Radiation 485

Fig. 1. Chain of the cellular event occurring in the cell/ tissue after ionizing radiation

exposure.

Radiation-induced DNA double-strand breaks are believed to be important lesions and the key trigger leading to a series of cellular consequences related to cell killing, gene mutation, induction of chromosome aberrations and carcinogenesis. There are two major cellular intrinsic factors deciding the extent of DNA damage in the irradiated cells, i.e. the activity of antioxidant systems and the capacity of DNA repair. There are two distinct but complementary mechanisms for DNA DSB repair namely; non-homologous end joining (NHEJ) and homologous recombination (HR) involving various repair proteins to execute the repair process. When discussing about a single or a group of radioprotectors, one has to keep in mind that radioprotective effect is an ability of radioprotectors to inhibit indirect effect and to repair direct and indirect damages occurred in the cells after radiation exposure. Discussions of all the molecular steps are out of the chapter's scope. In this chapter we are going to discuss a series of consequences happening after irradiation, types of damages induced, possible role of radioprotectors in preventing DNA damage and modulating DNA repair. At the end the future prospects for radioprotectors in mitigation of radiation damage will be discussed.
