Oxidative Stress-Induced Carcinogenesis
Oxygen is a blessing for the existence of all the aerobic organisms on earth. Nevertheless, it plays an adverse role in biological systems by involving the phenomenon of oxidative stress. In biological systems, oxygen constantly undergoes metabolic reacti
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Oxidative Stress-Induced Carcinogenesis
Oxidative Stress Oxygen is a blessing for the existence of all the aerobic organisms on earth. Nevertheless, it plays an adverse role in biological systems by involving the phenomenon of oxidative stress. In biological systems, oxygen constantly undergoes metabolic reactions to generate oxygen-derived free radicals in the form of superoxide (O2−), hydroxyl (OH), alkoxyl (RO), and peroxyl (RO2) plus non-radicals in the form of hydrogen peroxide (H2O2), peroxynitrite (ONOO–), hypochlorous acid (HOCl), and hypobromous acid (HOBr). Reactive species are divided into four groups depending on the main atom involved: ROS, reactive nitrogen species (RNS), reactive sulfur species (RSS), and reactive chloride species (RClS); their half-lives vary from a few nanoseconds to hours depending on the stability of the molecule. During intracellular metabolic processes like electron transport chain, ROS and RNS are also produced. Normal physiological state in a living system is achieved by a proper equilibrium between the generation and neutralization of ROS and does not lead to any oxidative damage (Roberts et al. 2009). A group of researchers illustrated that an imbalance between the generation of ROS (prooxidant) and antioxidant defense system leads to oxidative stress. This imbalance occurs due to two reasons: either by the attenuation in the elimination of ROS by oxidant defense mechanisms or by the overproduction of ROS such as the superoxide radical or hydroxyl radical (OH) which exhausts the endogenous antioxidant reservoirs in a cell. This excessive production of ROS alters and damages various intracellular molecules like DNA, RNA, lipids, and proteins by creating nicks in DNA, malfunctions in the DNA repair system, and DNA oxidation generating 8-hydroxy-2-deoxyguanosine, which has been reported to enhance aging and carcinogenesis by developing mutations in DNA (Roberts et al. 2010; Rashid et al. 2013a). Moreover, reactive species cause oxidation of cell membrane because it is vulnerable and rich in polyunsaturated lipids, thereby inducing lipid peroxidation and consequently enhancing the permeability of cell membrane leading to cell death. The most affected by reactive species are the proteins since they undergo © Springer Science+Business Media Singapore 2017 S. Rashid, Cancer and Chemoprevention: An Overview, DOI 10.1007/978-981-10-2579-2_7
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accumulation of thiol groups (−SH) and carbonyl groups (aldehydes and ketones) which get transformed into sulfur reactive radicals resulting in the modification of the protein structure and function. Furthermore, various enzymes such as cyclooxygenases, xanthine oxidase, uncoupled NOS, and NADPH oxidases enhance the production of ROS. Additionally various anticancer drugs, e.g., doxorubicin, 5-FU (Rashid et al. 2013b), and cisplatin (Khan et al. 2012), analgesics like acetaminophen (Ahmad et al. 2011); toxicants such as acrolein; heavy metals like As, Pb, Cd, and Hg; xenobiotics; ultraviolet
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