Chromium genotoxicity: A double-edged sword

Abstract

Certain forms of hexavalent chromium [Cr(VI)] are known respiratory carcinogens that induce a broad spectrum of DNA damage. Cr(VI)-carcinogenesis may be initiated or promoted through several mechanistic processes including, the intracellular metabolic reduction of Cr(VI) producing chromium species capable of interacting with DNA to yield genotoxic and mutagenic effects, Cr(VI)-induced inflammatory/immunological responses, and alteration of survival signaling pathways. Cr(VI) enters the cell through nonspecific anion channels, and is metabolically reduced by agents including ascorbate, glutathione, and cysteine to Cr(V), Cr(IV), and Cr(III). Cr(III) has a weak membrane permeability capacity and is unable to cross the cell membrane, thereby trapping it within the cell where it can bind to DNA and produce genetic damage leading to genomic instability. Structural genetic lesions produced by the intracellular reduction of Cr(VI) include DNA adducts, DNA strand breaks, DNA-protein crosslinks, oxidized bases, abasic sites, and DNA inter-and intrastrand crosslinks. The damage induced by Cr(VI) can lead to dysfunctional DNA replication and transcription, aberrant cell cycle checkpoints, dysregulated DNA repair mechanisms, microsatelite instability, inflammatory responses, and the disruption of key regulatory gene networks responsible for the balance of cell survival and cell death, which may all play an important role in Cr(VI) carcinogenesis. Several lines of evidence have indicated that neoplastic progression is a result of consecutive genetic/epigenetic changes that provide cellular survival advantages, and ultimately lead to the conversion of normal human cells to malignant cancer cells. This review is based on studies that provide a glimpse into Cr(VI) carcinogenicity via mechanisms including Cr(VI)-induced death-resistance, the involvement of DNA repair mechanisms in survival after chromium exposure, and the activation of survival signaling cascades in response to Cr(VI) genotoxicity.

Formation of Chromium-Containing Molten Salt Phase during Roasting of Chromite Ore with Sodium and Potassium Hydroxides

“…The landfilling of the COPR generated is an important source of hexavalent chromium, as the waste contains approximately 0.1-0.2 wt.% Cr 6+ which remains entrapped within the solid residue after water leaching. Hexavalent chromium is highly hazardous not only to human beings but also to aquatic environment, soil, flora and fauna [10], and therefore, the pollution-related problem associated with waste disposal is the main drawback of the alkali roasting process.…”

Punica granatum L. protects mice against hexavalent chromium-induced genotoxicity

“…The hexavalent form is usually linked with oxygen and is a strong oxidizing agent. Studies have shown that Cr(VI) is a mutagenic, carcinogenic and teratogenic agent, which easily penetrates the cell membrane in the form of chromate anion (Barceloux, 1999;Acharya et al, 2006;Nickens et al, 2010;Chang et al, 2011;Okello et al, 2012). Its molecular mechanisms of toxicity are not yet fully known, but it is believed that the intracellular increase in the production of reactive oxygen species (ROS) is probably a key factor in inducing cell damage (Ye et al, 1999;Wu et al, 2012).…”

“…It has been considered a potent occupational carcinogen among workers involved in electrodeposition, metal finishes/welding, wood preservatives, organic synthesis procedures and in leather tanning (Barceloux, 1999;Shrivastava et al, 2002;Acharya et al, 2006;Nickens et al, 2010). In such activities occupational exposure to Cr(VI)-contaminated dust and aerosols occurs predominantly through inhalation or skin contact (Zagrodzki et al, 2007).…”

Removal of airborne hexavalent chromium using alginate as a biosorbent

“…Hexavalent chromium, Cr (VI), has been classified as a human respiratory carcinogen and allergen (Ashley et al, 2003;Guertin et al, 2005;Hara et al 2010;Nickens et al, 2010). Long term exposure to airborne Cr (VI) has been known to cause ulceration and perforation of the nasal septum, bronchitis, asthma, and liver and kidney damages in exposed workers (Kumar et al, 2005;Costa and klein, 2006).…”