**4. Classification of radioprotective agents**

Radioprotective agent can be defined as "any agent that protects against radiation-induced damage, whether administered before, during, or after irradiation". They have been classified into three categories; *i. Prophylactic agents*, *ii. Mitigators*, and *iii. Therapeutic agents*  (Stone et al. 2004). Prophylactic agents are administered before radiation exposure to prevent damage. 'Mitigators' designates agents that are administered during or after radiation exposure with the aim of preventing or reducing the action of radiation on tissues before the appearance of symptoms. These agents include decorporation and chelating agents that mitigate injury from internal radionuclide exposure. They also include blocking agents that mitigate the uptake of radionuclides by specific organs; for example, potassium iodide (KI) protects the thyroid from radioiodine. Therapeutic agents are administered after radiation exposure to treat or facilitate recovery from various aspects of the acute radiation syndrome (ARS) and delayed effects of radiation exposure(Weiss and Landauer 2009). The

Ionizing radiation can produce different types of damage to DNA, RNA, proteins and other biomolecules. DNA is the major target of radiation induced damage where as membrane is an alternative target. Because the portion of water in living matter is quite high, radiolytic product of the water, mainly hydroxyl radical is responsible for most damages to biomolecules. Hydroxyl radical causes damages to biomolecules by abstracting an H-atom from the biomolecules (from the sugar moiety of the DNA or from the peptide chain of a protein) or by addition of the double bonds of aromatic moieties (DNA bases or aromatic

Ionizing radiation causes the formation of strand breaks in cellular DNA, as well as other types of lesions in the chromatin of cells(Roots et al. 1985). The amount of DNA damage induced is determined by type of radiation as well as the presence of other molecular components in close proximity to DNA, in particular the presence of proteins because it is well known that most molecular interactions between proteins and DNA occur via amino acids. It is estimated each gray (Gy) of radiation leads to about 100,000 ionizations within a cell, damage to over 1,000 bases, about 1,000 SSBs and about 20 – 40 DSBs. Despite this, 1 Gy kills only 30% of mammalian cells due to the effectiveness of DNA repair - particularly for

Lipid peroxidation has been found as the main damage to membrane lipids and lipoproteins. Ionizing radiation induced lipid oxidative modifications of poly unsaturated fatty acids (PUFAs) appears as a dynamic process initiated by hydroxyl free radicals generated by water radiolysis, amplified by a propagating-chain mechanism involving alkyl and peroxyl free radicals, and leading not only to hydroperoxides but also to a lot of other lipidic oxidized end-products, lipid hydroperoxides and conjugated dienes which are early

During ionizing radiation induced damage to protein, the type of reactions and consequences are quite similar to those of DNA; abstraction of H atoms and binding to aromatic rings, leading to backbone breakage and modification of side chains. All these event leads to peptide chain fragmentation and modification of amino acid side chain (e.g.Trp/formylkynurenine, Tyr/bityrosine,Cys/disulfide) (Spotheim-Maurizot and

Radioprotective agent can be defined as "any agent that protects against radiation-induced damage, whether administered before, during, or after irradiation". They have been classified into three categories; *i. Prophylactic agents*, *ii. Mitigators*, and *iii. Therapeutic agents*  (Stone et al. 2004). Prophylactic agents are administered before radiation exposure to prevent damage. 'Mitigators' designates agents that are administered during or after radiation exposure with the aim of preventing or reducing the action of radiation on tissues before the appearance of symptoms. These agents include decorporation and chelating agents that mitigate injury from internal radionuclide exposure. They also include blocking agents that mitigate the uptake of radionuclides by specific organs; for example, potassium iodide (KI) protects the thyroid from radioiodine. Therapeutic agents are administered after radiation exposure to treat or facilitate recovery from various aspects of the acute radiation syndrome (ARS) and delayed effects of radiation exposure(Weiss and Landauer 2009). The

**3. Types of damages induced after radiation exposure** 

moieties of protein side chain) (Spothem-Maurizot et al. 2008).

products of lipid peroxidation (Spothem-Maurizot et al. 2008).

non-DSB lesions (Spothem-Maurizot et al. 2008).

**4. Classification of radioprotective agents** 

Davidkova 2011).

putative mechanism of radioprotection by plant and herbal radioprotectors may be mediated through several mechanisms, since they are complex mixtures of many chemicals (Jagetia 2007) but this may or may not be true with the pure compounds. Table 1 is a list of some radioprotective agents with their possible radioprotective properties.


Role of Radioprotectors in the Inhibition of DNA Damage

**5.1 Alpha tocopherol monoglucoside (TMG)** 

these molecules are given below.

(Cherdyntseva et al. 2005).

pathway (Lee et al. 2011).

**5.3 Caffeine** 

**5.2 Baicalein** 

and Modulation of DNA Repair After Exposure to Gamma-Radiation 489

flavonoid troxerutin, ferulic acid present in cereals, the food flavoring agent vanillin and tocopherol-mono-glucoside among others as effective radioprotectors. Details of some of

TMG, a water-soluble derivative of Vitamin E, has been reported to be a good radioprotector with low toxicity (Kapoor et al. 2002; Nair et al. 2004; Rajagopalan et al. 2002). It has been reported that an oral administration of 2 g/kg body weight of TMG, five minutes prior to radiation exposure, resulted in early recovery of the radiation-induced weight loss (Nair et al. 2003). Embryonic death, resulting from exposure to 2 Gy radiation in pregnant mice, was reduced by 75% with a single intra peritoneal injection of TMG (0.6 g/kg body weight) prior to the radiation exposure. However, the administration of TMG after the radiation exposure did not have any effect on the embryonic mortality (Nair et al. 2003). A single intra peritoneal injection of TMG (0.6 g/kg) to mice, after whole body irradiation, elevated the LD50 (30) from 6 to 6.72 Gy (Nair et al. 2003). Radiation induced formation of micronucleated polychromatic and normochromatic erythrocytes in mouse bone marrow cells was inhibited by a single injection of TMG (0.6 g/kg body weight) i.p. after the radiation exposure with a dose reduction factor of 0.5 (Satyamitra et al. 2001). Our in vitro studies, either with humans or mice, peripheral blood leucocytes showed that the presence of TMG (0.5 mM) in post-irradiation incubation medium did not enhance the repair of DNA strand breaks(Salvi et al. 2007). TMG is also effective in preventing radiation-induced bone marrow death in mice and enhance hematopoietic recovery (Ueno et al. 2009),

Baicalein (scheme 2A), has been reported to possess lipid peroxidation inhibitory activity. Our results indicate that baicalein is a potent radioprotector at micromolar (5-50) levels. The protective effect, at 5 μM, was 80% against formation of thiobarbituric acid reactive substances (TBARS) and 50% against lipid hydroperoxide. The protective ability against protein carbonyl formation was 50% and protein hydroperoxide formation 85% at the same concentration. Similar protective effects were also observed against damage to glutathione peroxidase and superoxide dismutase. A concentration dependent effect also was seen with most of the parameters examined. Single-strand break formation induced by radiation also was accentuated with baicalein. It also inhibited the DNA binding caused by radiation. (Tilak and Devasagayam 2003). Recently it was found that baicalein has a radioprotective effect against NF-κB-mediated inflammatory response through MAPKs and the Akt

Caffeine is a bitter, white crystalline xanthine alkaloid that is a psychoactive stimulant present in coffee and cola-based soft drinks. In humans, caffeine acts as a central nervous system (CNS) stimulant, temporarily warding off drowsiness and restoring alertness. We have shown that caffeine protected against DNA strand breaks in plasmid pBR322, a system devoid of repair and replication machinery (Kumar et al. 2001). This protective effect was related to the demonstrated antioxidant properties of caffeine in vitro, including scavenging of primary and secondary ROS (Devasagayam et al. 1996). Pretreatment with caffeine at


Table 1. A list of well known radioprotectors, mitigators and therapeutics.
