Oxidative stress and metal carcinogenesis

Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536, USA.
Free Radical Biology and Medicine (Impact Factor: 5.74). 06/2012; 53(4):742-57. DOI: 10.1016/j.freeradbiomed.2012.06.002
Source: PubMed


Occupational and environmental exposures to metals are closely associated with an increased risk of various cancers. Although carcinogenesis caused by metals has been intensively investigated, the exact mechanisms of action are still unclear. Accumulating evidence indicates that reactive oxygen species (ROS) generated by metals play important roles in the etiology of degenerative and chronic diseases. This review covers recent advances in (1) metal-induced generation of ROS and the related mechanisms; (2) the relationship between metal-mediated ROS generation and carcinogenesis; and (3) the signaling proteins involved in metal-induced carcinogenesis, especially intracellular reduction-oxidation-sensitive molecules.

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    • "Catalytic ferrous iron (catalytic Fe(II)) reacts with hydrogen peroxide to produce the hydroxyl radical in a Fenton reaction [11] [12]. Hydroxyl radicals not only react with lipids and proteins but also causes oxidative damage to DNA, resulting in base modifications and strand breaks [13] [14] [15] [16]. Endometriotic cysts present extremely high concentrations of catalytic iron compared with normal serum and the contents of other ovarian tumors. "
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    • "A high cellular oxidative load in lung tissues may result from an environmental perturbation such as particulate exposure and can disrupt the normal cellular redox state (Georgakilas 2012; Klaunig et al., 2010; Klaunig et al., 2011). Vanadium compounds formed in tissues from V 2 O 5 , including vanadate, may induce oxidative stress in vivo (Lee et al., 2012; Kulkarni et al., 2014). For instance, V 2 O 5 nanoparticles in a nose-only inhalation exposure in male Wistar rats showed transient oxidative stress and VO 2 nanoparticles produce persistent oxidative stress (Kulkarni et al., 2014). "
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    • "This could be explained by an increased production of hydrogen peroxide in quantities exceeding SOD and GPx antioxidant capacities, resulting in their activity inhibition (Atli et al., 2006). It was previously described that lead and/ or cadmium exposure induced oxidative stress by the inhibition of GPx activity (Flora et al., 2012; Lee et al., 2012). Taking into account gender, the decrease in GPx activity is even more pronounced among exposed men (Fig. 2E). "
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