Abstract:Nickel (Ni) is known to be a major carcinogenic heavy metal. Occupational and environmental exposure to Ni has been implicated in human lung and nasal cancers. Currently, the molecular mechanisms of Ni carcinogenicity remain unclear, but studies have shown that Ni-caused DNA damage is an important carcinogenic mechanism. Therefore, we conducted a literature search of DNA damage associated with Ni exposure and summarized known Ni-caused DNA damage effects. In vitro and vivo studies demonstrated that Ni can indu… Show more
“…In the current study, in order to investigate the cytotoxicity and immune response caused by exposure to low concentrations of the heavy metals, Ni and Cd, which are known to have cytotoxicity and cause immune toxicity [ 8 , 9 ], were selected. Ni generally enters cells through transferrin or divalent metal transporter-1 (DMT1) and exhibits cytotoxicity by inhibiting DNA repair processes or causing oxidative stress through the depletion of intracellular antioxidants such as glutathione [ 16 , 17 ]. Cd enters cells through the ZIP (ZRT, IRT-like protein) transporter, metallothionein, and DMT1 (divalent metal transporter-1).…”
Section: Discussionmentioning
confidence: 99%
“…Our results showed that 50 nM of Ni and 10 nM of Cd alone did not have a significant effect on cell viability; however, when the two heavy metals were used in mixture at these concentrations, cell viability was significantly lower than that of the control group after 48 h. Studies on the synergic [ 23 , 24 ] and antagonistic [ 25 , 26 ] effects of heavy metal co-exposure have been conducted, and their results suggest that the mixed exposure of Ni and Cd has a synergic effect on cell viability. Differences in cell entry and cytotoxic mechanisms of Ni and Cd [ 16 , 17 , 18 , 19 , 20 , 21 , 22 ] have been identified; therefore, their individual properties may be related to these synergic effects.…”
Environmental exposure to low concentrations of heavy metals is common in the general population, but the toxicity, immune response mechanisms, and the effects of single and mixed metal exposures have not been clearly identified. In this study, A549 cells and Raw264.7 cells were exposed to low concentrations of the heavy metals nickel (Ni) and cadmium (Cd) for 24, 48, and 72 h, and then cell viability and cytokine levels were analyzed. We found that exposure to low concentrations of Ni (50 nM) or Cd (10 nM) alone did not affect cell viability. However, mixing them together decreased cell viability. In addition, the levels of IL-10, IL-12, and TNF-α decreased with single (only Cd) and mixed (Ni and Cd) exposures. These results show that exposure to low concentrations of heavy metals could affect the normal immune response, even without obvious clinical manifestations. Therefore, chronic exposure to heavy metals might have adverse effects on overall health.
“…In the current study, in order to investigate the cytotoxicity and immune response caused by exposure to low concentrations of the heavy metals, Ni and Cd, which are known to have cytotoxicity and cause immune toxicity [ 8 , 9 ], were selected. Ni generally enters cells through transferrin or divalent metal transporter-1 (DMT1) and exhibits cytotoxicity by inhibiting DNA repair processes or causing oxidative stress through the depletion of intracellular antioxidants such as glutathione [ 16 , 17 ]. Cd enters cells through the ZIP (ZRT, IRT-like protein) transporter, metallothionein, and DMT1 (divalent metal transporter-1).…”
Section: Discussionmentioning
confidence: 99%
“…Our results showed that 50 nM of Ni and 10 nM of Cd alone did not have a significant effect on cell viability; however, when the two heavy metals were used in mixture at these concentrations, cell viability was significantly lower than that of the control group after 48 h. Studies on the synergic [ 23 , 24 ] and antagonistic [ 25 , 26 ] effects of heavy metal co-exposure have been conducted, and their results suggest that the mixed exposure of Ni and Cd has a synergic effect on cell viability. Differences in cell entry and cytotoxic mechanisms of Ni and Cd [ 16 , 17 , 18 , 19 , 20 , 21 , 22 ] have been identified; therefore, their individual properties may be related to these synergic effects.…”
Environmental exposure to low concentrations of heavy metals is common in the general population, but the toxicity, immune response mechanisms, and the effects of single and mixed metal exposures have not been clearly identified. In this study, A549 cells and Raw264.7 cells were exposed to low concentrations of the heavy metals nickel (Ni) and cadmium (Cd) for 24, 48, and 72 h, and then cell viability and cytokine levels were analyzed. We found that exposure to low concentrations of Ni (50 nM) or Cd (10 nM) alone did not affect cell viability. However, mixing them together decreased cell viability. In addition, the levels of IL-10, IL-12, and TNF-α decreased with single (only Cd) and mixed (Ni and Cd) exposures. These results show that exposure to low concentrations of heavy metals could affect the normal immune response, even without obvious clinical manifestations. Therefore, chronic exposure to heavy metals might have adverse effects on overall health.
“…The International Agency for Research on Cancer (IARC) identified nickel compounds as Class I carcinogenic materials 1,2 . But the toxicity of nickel oxide (NiO) did not attract much attention until the rise of nanotechnology.…”
Nickel oxide nanoparticles (NiO NPs) causes pulmonary fibrosis via activating transforming growth factor-β1 (TGF-β1) in rats, but its upstream regulatory mechanisms are unknown. This study aimed to explore the role of long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) in NiO NPs-induced collagen deposition. Male Wistar rats were intratracheally instilled with NiO NPs (0.015, 0.06, and 0.24 mg/kg b.w.) twice a week for 9 weeks. Human lung adenocarcinoma epithelial cells (A549 cells) were cultured with NiO NPs (25, 50, and 100 μg/ml) to establish collagen deposition model. We discovered that NiO NPs-induced rat pulmonary fibrosis was accompanied by the epithelial-mesenchymal transition (EMT) occurrence and MEG3 down-regulation in rat lung tissues. In cell collagen deposition model, NiO NPs also evoked EMT and decreased MEG3 expression in a dose-dependent manner in A549 cells. By overexpressing MEG3 in A549 cells, we found that MEG3 inhibited the level of TGF-β1, EMT process and collagen formation. Moreover, our data showed that SB431542 (TGF-β1 inhibitor) had an inhibitory effect on NiO NPs-induced EMT and collagen formation. Our results indicated that MEG3 inhibited NiO NPs-induced collagen deposition by regulating TGF-β1-mediated EMT process, which may provide some clues for insighting into the mechanisms of NiO NPs-induced pulmonary fibrosis.
“…There appears to be less within-group variation in BEAS-2B group. All these heavy metals and metalloid are directly or indirectly associated with the development of lung cancer [ [94] , [95] , [96] , [97] ]. Fig.…”
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