Recent advances in metal carcinogenicity

Abstract

The carcinogenicity of nickel, chromium, arsenic, cobalt, and cadmium compounds has long been recognized. Nevertheless, the mechanisms involved in tumor formation are not well understood. The carcinogenic potential depends on metal species; major determinants are oxidation state and solubility. Two modes of action seem to be predominant: the induction of oxidative DNA damage and the interaction with DNA repair processes, leading to an enhancement of genotoxicity in combination with a variety of DNA-damaging agents. Nucleotide excision repair (NER) is inhibited at low, non-cytotoxic concentrations of nickel(II), cadmium(II), cobalt(II), and arsenic(III); the repair of oxidative DNA base modifications is disturbed by nickel(II) and cadmium(II). One reason for repair inhibition appears to be the displacement of zinc(II) and magnesium(II). Potentially sensitive targets are so-called zinc finger structures present in several DNA repair enzymes such as the mammalian XPA protein and the bacterial formamidopyrimidine-DNA glycosylase (Fpg protein); detailed studies revealed that each zinc finger protein exerts unique sensitivities toward toxic metal ions. Taken together, toxic metal ions may lower the genetic stability by inducing oxidative DNA damage and by decreasing the repair capacity towards DNA lesions induced by endogenous and exogenous mutagens, which may in turn increase the risk of tumor formation. CARCINOGENIC METAL COMPOUNDS: OCCURRENCE, CHEMICAL SPECIATION, AND INTERFERENCE WITH CELLULAR FUNCTION RELATED TO CARCINOGENICITYMetal compounds are part of the earth crust and thus ubiquitously distributed in the environment. Yet, combustion and industrial use contribute significantly to human exposure at workplaces and in the general environment. Some metals, including chromium, nickel, arsenic, cadmium, and cobalt, have long been recognized as human and/or animal carcinogens [1][2][3][4]. Their carcinogenic potentials depend largely on factors like oxidation state and solubility. Thus, exposure to chromium(VI) is strongly associated to human lung cancer, while chromium(III) is largely inactive. This discrepancy is related to differences in bioavailability; while chromium(III) is unable to cross the cell membrane, chromium(VI) is readily taken up by anion transporter followed by intracellular reduction to chromium(III) (reviewed in ref. 5).The impact of solubility is most evident for nickel compounds. While particulate nickel compounds with intermediate water solubility (like nickel subsulfide) are strong carcinogens, soluble nickel(II) salts exert considerably weaker effects. This difference could be attributed to differences in bioavailability. While water-soluble nickel salts are taken up only slowly by cells, particulate nickel compounds are phagocytosed and gradually dissolved in lysosomes because of the low pH, yielding high concentrations of nickel ions in the nucleus [6]. Nevertheless, the underlying molecular mechanisms of metal carcinogenicity are not well understood, especially since they are n...

Elemental fingerprinting of tumorous and adjacent non-tumorous tissues from patients with colorectal cancer using ICP-MS, ICP-OES and chemometric analysis

“…Inconsistent results on Cd in tumorous tissues have been published. Higher contents in breast (Ionescu et al 2006) and lung (Martin Mateo et al 1990) tumorous tissues have been found in comparison to non tumorous tissues. No differences have been found in liver (Mai et al 2006), lung (Kuo et al 2006) or colon (Martin Mateo et al 1990).…”

“…Comparative studies carried out recently on normal and cancerous human tissues report controversial results, especially for some elements such as Cu, Fe, Ni, Se and Zn. In general, most of authors found significantly elevated concentrations or non-differences for several elements in malignant tissues (Raju et al 2006;Ionescu et al 2006;Ebrahim et al 2007), however, decreases in concentration have also been reported (Zoriy et al 2006).…”

“…Many studies have targeted metal-induced carcinogenicity, emphasising their role in the generation of oxygen-free radicals (Halliwell and Gutteridge 1999;Leonard et al 2004;Valko and Morris 2005). These radicals can cause changes in DNA bases, enhanced lipid peroxidation and homeostasis.…”

X-Ray Studies and Antibacterial Activity in Copper and Cobalt Complexes With Imidazole Derivative Ligands

“…Many inorganic complexes show antitumor and antibacterial activity. [7][8][9][10][11][12] There are numerous copper(II) compounds that present biological activity as antiinflammatory, anticonvulsive, antifungal, antibacterial, and antimicrobial agents. [13][14][15][16][17][18] An example is the trans-bis(acetate)bis(imidazole)copper(II) complex, which exhibits the strongest antitumor activity against the mouse melanoma cancer cell line B16.…”

In vivo genotoxic effects of industrial waste leachates in mice following oral exposure

“…Individual metals also affect genetic stability and inhibit systems that repair the DNA damage induced by endogenous and exogenous mutagens [Hartwig, 1998[Hartwig, , 2000. For instance, low concentrations of nickel are known to produce deleterious effects by catalyzing the genotoxic effects of other toxic metals [Costa et al, 1994].…”