ABSTRACT
Ionizing radiation, with low linear energy transfer (LET) in the biological system, is an important source for the generation of oxygen-derived reactive oxygen species (ROS) and excited states (Von Sonntag, 1987). As such, there is considerable amount of water in all cells apart from the target macromolecules DNA, protein, lipids, etc. Exposure to ionizing radiation results in a radiolytic cleavage of water, giving rise to e~q OH# and H‘ (Kesavan, 1992; Von Sonntag, 1987). Oxygen, in view of its bi-radical nature, is the most important electron acceptor present in aerobic cells. Oxygen rapidly accepts unpaired electrons and gives rise to a series of partially-reduced ROS such as superoxide (O“ ), hydroxyl (OH#), and peroxyl (ROO*) radicals (Kesavan, 1992; Von Sonntag, 1987). The formation of O 2 takes place by energy transfer reactions as also by the action of hydroperoxyl with superoxide (Kesavan, 1992). Due to the presence of polyunsaturated fatty acids, membranes are highly prone to oxidative damage by ROS (Giusti et al., 1998). Radiation-induced ROS may cause lipid peroxidation and a loss of structural and functional integrity of the membranes, leading directly to cytotoxicity or indirectly to genotoxicity. Oxidative damage is implicated in ageing and several diseases (Burcham, 1998; Shao et al., 1996). In recent years, much attention has been focussed on this subject, especially in the field of clinical medicine, due to its relevance in degenerative diseases (Sies, 1996; Thomas and Kalyanaraman, 1998). It is now a well-established fact that ROS are important in the modification of proteins leading to oxidation of amino acid side chain residues, cleavage of peptide bonds, and formation of covalent protein-
protein cross-linked derivatives (Dean et al., 1997; Stadtman and Berlett, 1997). Oxidized proteins, if they are not degraded by endogenous proteases, accumulate, resulting in ageing and various disorders (Stadtman and Berlett, 1997). Although there are several antioxidant defense mechanisms in the form of chemicals or enzymes (Packer and Ong, 1998), including those present in cells, they are overwhelmed by the high levels of prooxidants generated during radiation. Hence, compounds protecting against ionizing radiation will have potential benefits as radioprotectors. In current years, the information regarding antioxidant defenses by vitamins E and C, protecting membranes against ROS-induced damage, has been well documented (Packer and Ong, 1998). We have also recently shown nicotinamide (vitamin B3) as an antioxidant against oxidative damage in subcellular membranes (Kamat and Devasagayam, 1996).
