Abstract
Worldwide, several million workers are employed in the various chromium (Cr) industries. These workers may suffer from a variety of adverse health effects produced by dusts, mists and fumes containing Cr in the hexavalent oxidation state, Cr(VI). Of major importance, occupational exposure to Cr(VI) compounds has been firmly associated with the development of lung cancer. Counterintuitively, Cr(VI) is mostly unreactive towards most biomolecules, including nucleic acids. However, its intracellular reduction produces several species that react extensively with biomolecules. The diversity and chemical versatility of these species add great complexity to the study of the molecular mechanisms underlying Cr(VI) toxicity and carcinogenicity. As a consequence, these mechanisms are still poorly understood, in spite of intensive research efforts. Here, we discuss the impact of Cr(VI) on the stress response—an intricate cellular system against proteotoxic stress which is increasingly viewed as playing a critical role in carcinogenesis. This discussion is preceded by information regarding applications, chemical properties and adverse health effects of Cr(VI). A summary of our current understanding of cancer initiation, promotion and progression is also provided, followed by a brief description of the stress response and its links to cancer and by an overview of potential molecular mechanisms of Cr(VI) carcinogenicity.
Highlights
Hexavalent ChromiumChromium (Cr), a transition metal, is the 21st most abundant chemical element in Earth’s crust
Postmortem microscopic analysis of lung tissue and biopsy samples from chromate industry workers revealed that particulate Cr(VI) compounds tend to deposit at the bronchial bifurcations [13,14,15]
These findings suggest that Cr(III)-DNA adduct formation contributes to the TP53 mutations observed in lung carcinogenesis [127]
Summary
Chromium (Cr), a transition metal, is the 21st most abundant chemical element in Earth’s crust. The different toxicities of Cr(III) and Cr(VI) compounds can be rationalized in terms of their physico-chemical properties Their ability to cross biological membranes and, induce intracellular damage is determined by their sizes, structures and charges. As mutations often disrupt a protein’s ability to fold [28], accumulation of increasingly larger amounts of mutated proteins represents yet another type of cell intrinsic stress—proteotoxic stress [29] (Figure 1). This type of stress can be created by any structural alteration that may lead to protein misfolding and aggregation. Malignant tumors are characterized by rampant chromosomal instability and aneuploidy, caused by chromosome segregation errors during mitosis Such extensive damage leads to genotoxic stress. While genotoxic stress leads to p53-induced apoptosis in normal cells, in malignant cells it is tolerated and subverted, giving rise to a mosaic of genomic mutations and karyotypic abnormalities in solid tumors [37,38,39]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
