Chromium (VI)-induced transformation is enhanced by Zn deficiency in BALB/c 3T3 cells

Abstract

-Hexavalent chromium [Cr(VI)] is a carcinogenic heavy metal that is reduced to intermediate oxidation states, such as Cr(V) and Cr(IV), in the process of forming stable Cr(III) forms; it is these intermediate forms that are thought to be responsible for much of the DNA damage and mutations that are induced by Cr(VI). Metallothionein (MT), a heavy metal-binding protein, is induced by zinc and other heavy metals and protects cells from the toxic effects of these metals by sequestering them. MT cannot bind Cr, but by scavenging reactive oxygen species through its cysteine residues, it may act as a protective factor against Cr(VI)-induced DNA lesions by reducing Cr(VI) directly to Cr(III), thereby avoiding the creation of the toxic intermediates. Here, we showed that Zn deficiency decreased MT expression in BALB/3T3 clone A31-1-1 cells and caused them to become highly susceptible to Cr(VI)-induced transformation. To obtain Zn-deficient cultures, cells were cultured in medium supplemented with 10% Chelex ® -100 chelating resin-treated FBS. The increase in susceptibility to transformation was abolished by culturing the cells with supplemental Zn (50 μM). Previously, we reported that Cr(VI) inhibits MT transcription by preventing the zinc-dependent formation of a complex of metal response element-binding transcription factor-1 (MTF-1) and the co-activator p300. Our results suggest that the carcinogenicity of Cr(VI) is enhanced by MTF-1 dysfunction.

Adverse effects of parental zinc deficiency on metal homeostasis and embryonic development in a zebrafish model

“…Also, given MTF-1’s important role in regulating metallothioneins and metal homeostasis in relationship to heavy metal exposure, it is possible that zinc deficiency, either in the parent or the embryo, may cause embryos to be more sensitive to toxic metals. In support of this possibility, zinc deficient cells in culture are more sensitive to hexavalent chromium exposure [64]. An important area of future research would be to examine subcellular localization of MTF-1 or altered metal-response-element binding in response to zinc deficiency to understand the functional perturbations in MTF-1.…”

Rationale for the Successful Management of EDTA Chelation Therapy in Human Burden by Toxic Metals

“…Other less-common toxic metals are antimony (Sb), barium (Ba), beryllium (Be), bismuth (Bi), cesium (Cs), gadolinium (Gd), palladium (Pd), platinum (Pt), tellurium (Te), thallium (Tl), thorium (Th), tin (Sn), tungsten (W), and uranium (U); Cr is a carcinogenic heavy metal responsible for DNA damage and mutations [42]. Table 1 reports (for each toxic metal) the target organs and/or apparatus, the sources of toxic metals (which are always represented by ingestion, inhalation, or dermal absorption; of note, gadolinium, when used as contrast agent, and platinum, when used as chemotherapeutic agent, could be IV administered), and the toxic doses of each metal.…”

Toxicology of organic-inorganic hybrid molecules: bio-organometallics and its toxicology

“…and metalloids. Such studies published these past three years in the Journal of Toxicological Sciences investigated the toxicity of many types of metals, including cadmium (Ohtani et al, 2013;Miura et al, 2013;Baba et al, 2014;Du et al, 2014;Park et al, 2015;Lukkhananan et al, 2015), mercury (Yoshida et al, 2013;Kim et al, 2014), methylmercury (Hwang et al, 2013a(Hwang et al, , 2013bIwai-Shimada et al, 2013;Chang et al, 2013;Hirooka et al, 2013;Kim et al, 2013;Watanabe et al, 2013;Shao et al, 2015;Toyama et al, 2015), aluminum (Zhang et al, 2013;Jinzhu et al, 2015), manganese (Fujishiro et al, 2013), uranium (Lestaevel et al, 2013), arsenic (Tokumoto et al, 2013;Wang et al, 2015), arsine (Kato et al, 2014), organic bismuth (Kohri et al, 2015), chromium (Kimura et al, 2015), and tributyltin (Oyanagi et al, 2015). Although methylmercury is one of the organic-inorganic hybrid molecules (the minimum unit!…”