Oxidative Stress and Oxidative Damage in Carcinogenesis

Abstract

Carcinogenesis is a multistep process involving mutation and the subsequent selective clonal expansion of the mutated cell. Chemical and physical agents including those that induce reative oxygen species can induce and/or modulate this multistep process. Several modes of action by which carcinogens induce cancer have been identified, including through production of reactive oxygen species (ROS). Oxidative damage to cellular macromolecules can arise through overproduction of ROS and faulty antioxidant and/or DNA repair mechanisms. In addition, ROS can stimulate signal transduction pathways and lead to activation of key transcription factors such as Nrf2 and NF-kB. The resultant altered gene expression patterns evoked by ROS contribute to the carcinogenesis process. Recent evidence demonstrates an association between a number of single nucleotide polymorphisms (SNPs) in oxidative DNA repair genes and antioxidant genes with human cancer susceptibility. These aspects of ROS biology will be discussed in the context of their relationship to carcinogenesis.

Roles of Oxidative Stress in the Development and Progression of Breast Cancer

“…External sources of ROS can be environmental pollution, radiation, optical radiation, and chemical compounds including anticancer drugs, smoking, and alcohol (Valko et al, 2006;Aldini et al, 2010;Sosa et al,2013). Reactive oxygen species include superoxide anion (O2 -), hydroxyl radical (OH), and hydrogen peroxide (H 2 O 2 ) as the most reactive hydroxyl radicals, and ROS is generated from H 2 O 2 and metals such as iron via the Fenton reaction (Noda et al, 2001;Barrera, 2006;Klaunig et al, 2010). The first and most important ROS in the body is superoxide anion, which is generated during oxidative phosphorylation reactions and electron transport along with a respiratory chain in the mitochondrial inner membrane (the main source of ROS).…”

“…One common product of oxidative damage to DNA and a main marker of oxidative stress is 8-hydroxyguanosine (8-OHdG), which accumulates in breast tumor cells. Therefore, it may be useful in clinical diagnoses and can be used as a tumor marker (Yoshikawa and Naito, 2002;Klaunig et al, 2010). Glutathione is an antioxidant and reducing compound in the body which exists in two forms: resuscitation (GSH) and oxidized (GSSG).…”

“…The characteristics of cancer cells include loss of contact inhibition, resistance to apoptosis, and insensitivity to cell growth arrest signals. Angiogenesis is a chief characteristic of cancer cells (Visvader and Lindeman, 2008;Klaunig et al, 2010;Fiaschi and Chiarugi, 2012;Siegel et al, 2013).…”

Association between Vegetable, Fruit and Carbohydrate Intake and Breast Cancer Risk in Relation to Physical Activity

“…Growing evidence indicates that too intense or sporadic exercise training can promote the formation of cytotoxic reactive oxygen species (ROS) in muscle that induce disturbance cellular redox balance in muscle (Davies et al, 1982;Powers et al, 2004;Sarma et al, 2010). The role of oxidative stress in breast cancer development was addressed in several studies (Thomson, 1994;Brown and Bicknell, 2001;Klaunig et al, 2010;Clague and Bernstein, 2012). In contrast, nonexhaustive exercise reduces sex hormone levels (Alegre et al, 2013), the production of ROS, improves antioxidant defense system and enhances the resistance of tissues against these species (reviewed by Kruk, 2011).…”

Antioxidant and antidiabetic properties of tartary buckwheat rice flavonoids after in vitro digestion

“…Oxidative stress instigated by reactive oxygen species (ROS) leads to mutations and DNA damage , which further leads to the development of chronic disorders and age-related diseases (Khansari et al, 2009;Klaunig et al, 2010;Chen et al, 2012b;Rahman et al, 2012). Oxidative stressinduced cellular dysfunction occurs when endogenous antioxidant defence mechanisms and DNA repair systems are overwhelmed.…”