# A Review on Potential Antimutagenic Plants of Saudi Arabia
## 2 How Does Oxidative Stress Contribute to Mutation? Normal oxidative metabolism in the cells causes the formation of reactive oxygen species (ROS) and they are known to play a role in both physiological and pathological changes in the body. The beneficial action of ROS occurs when cells are exposed to unpleasant situations such as noxia and infection. These responses include activation of the cellular signalling system and usually take place at a low/moderate level of ROS. The harmful effect of these species is termed oxidative stress and could damage biological systems due to over-production of free radicals [14]. Damaging effects were found to occur in almost all the cellular components, including nucleic acids, proteins, and lipids. Ageing, metabolic diseases, cancer and inflammatory reactions are a few of the important pathological changes that occur due to oxidative modification of biomolecules [15]. As has been reported, lipid peroxidation could be both a free radical-mediated process as well as a source of secondary free radicals. These free radicals are known to perform the function of second messengers, directly react with other organelles and/or diffuse into surrounding tissues to spread the lesion [16]. Previous research indicated that lipid peroxidation is associated with the destruction of lipid membranes and is found to be high in patients with diabetes, ischemic reperfusion injury, Alzheimer's disease, and autoimmune diseases [17]. The oxidative damage of proteins is reported to occur in three pathways: reaction with oxidative products of lipids and carbohydrates, amino acid residue modification and peptide cleavage [18]. Proteins containing arginine, cysteine, methionine, cystine, tryptophane, tyrosine and histidine are considered to be the most vulnerable to oxidative damage. Occurrences of age-related diseases such as arthritis and Alzheimer's have been strongly linked to the oxidative damage of proteins [19]. Several studies conducted in the past have demonstrated that nuclear components such as DNA and RNA are vulnerable to oxidative damage. Damage to RNA will interfere with protein synthesis, whereas DNA injuries are reported to be a major cause of age-related diseases and cancer [20]. The studies suggest that DNA damage includes strand breaks (single/double), cross linking of bases, modification of purine and pyrimidine bases. The most common free radicals that are known to damage DNA include hydroxyl radical (\(\bullet\)OH), superoxide anions (O\({}_{2}\)\({}^{\bullet-}\)), hydrogen peroxide (H\({}_{2}\)O\({}_{2}\)), malondialdehydedehyde (MDA), xanthine oxidase (XO) and reactive nitrogen species (RNS) [21]. Earlier studies showed that O\({}_{2}\)\({}^{\bullet-}\) interferes with enzyme functions, increases the proliferation of B-lymphocytes, and causes peroxidation of unsaturated lipids. H\({}_{2}\)O\({}_{2}\) is a potent oxidant, possessing the ability to kill any cell, and can induce changes in the proliferation of cells by activating the NF-\(\kappa\) B [22]. One of the most unstable free radicals is \(\bullet\)OH, which can react with any molecule in the cell, such as nucleic acids, proteins, polysaccharides, and lipids. While MDA is formed from lipid peroxidation and prostaglandin biosynthesis, its production is reported to be associated with carcinogenesis [23]. Further, XO is found to be cytotoxic and produce a considerable amount of O\({}_{2}\)\({}^{\bullet-}\) that has the tendency to cause DNA-strand breaks [24]. In addition, inflamed tissues have been reported to produce nitric oxide and its derivatives. These components can contribute to carcinogenesis by inducing DNA breaks and can also act as a source of mutagens [25]. It is observed that almost all cells will undergo DNA damage after exposure to oxidative stress. All the damage need not necessarily lead to mutation/cancer. The damage of lower magnitude is reported to be efficiently repaired while highly damaged cell undergoes apoptosis.