Distinct mechanisms of oxidative DNA damage induced by carcinogenic nickel subsulfide and nickel oxides.

Abstract

The U.S. National Toxicology Program has shown clear evidence of carcinogenicity of nickel subsulfide (Ni(3)S(2)) and some evidence of carcinogenicity of NiO (green) in rats. In the present study, DNA damage in cultured cells and in lungs of rats induced by nickel compounds was investigated to clarify the mechanism of nickel carcinogenesis. In cultured HeLa cells, Ni(3)S(2) induced a significant increase in 8-hydroxydeoxyguanosine (8-OH-dG) formation, whereas NiO (black), NiO (green), and NiSO(4) did not. On the other hand, in rats, intratracheal instillation of all these nickel compounds significantly increased 8-OH-dG content in the lungs. The disparities in DNA damage between cultured cells and animals could be accounted for by two different mechanisms for nickel-induced oxidative DNA damage in lungs of rats. One is direct oxidative DNA damage: Ni(II) enters the cells and then reacts with endogenous and/or nickel sulfide-produced hydrogen peroxide (H(2)O(2)) to give reactive oxygen species that cause DNA damage. This mechanism is supported by oxidative damage to isolated DNA treated with Ni(II) and H(2)O(2). The other mechanism is indirect oxidative DNA damage due to inflammation. This double mechanism for DNA damage may explain the relatively high carcinogenic risk associated with Ni(3)S(2).

Systemic and Local Tissue Response to Titanium Corrosion

“…It is known that trace metals can increase physiological production of reactive oxygen species (ROS) which, without a compensatory increase in antioxidative species, can lead to tissue damage (Gottschling et al, 2002;Kawanishi et al, 2002;Maziere et al, 2003). Studies conducted at our laboratory have shown the presence of titanium and zirconium particles in alveolar phagocytes immunohistochemically identified as CD68 macrophages (Olmedo et al, 2008b).…”

Cytotoxicity and apoptotic effects of nickel oxide nanoparticles in cultured HeLa cells.

“…To date, most nanotoxicity research has been focused on individual nano-sized metal oxides. The potential toxicity of nanoparticles, including nickel oxide (NiO), titanium dioxide (TiO 2 ), carbon nanotubes, and fullerenes, has drawn significant attention [13][14][15][16]. For example, NiO particles have been shown to trigger reactive oxygen species (ROS) that cause DNA damage in lungs of rats [13].…”

Remodeling of heterochromatin induced by heavy metals in extreme old age

“…Aluminum and copper accumulate in the tissues of old humans and animals and presumably act as binding agents that mediate euand heterochromatin condensation. Thus, they may explain rising mutation rates and structural changes of chromosomes (Jokhadze and Lezhava 1994;Kawanishi et al 2002;Theophanides and Anastassopoulou 2002). Cu(II) induces conformational changes (condensation) in the chromosomes exposed on the cells of Chinese hamster ovaries.…”