Oxidative damage and OGG1 expression induced by a combined effect of titanium dioxide nanoparticles and lead acetate in human hepatocytes

Du, Hongwu; Zhu, Xiaonian; Fan, Chuangang; Xu, Song; Wang, Youjie; Zhou, Yikai

doi:10.1002/tox.20682

Cited by 38 publications

(19 citation statements)

References 52 publications

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“…Immortalized Ogg1-/- MEFs (KO) stably transfected with WT Ogg1 or S326C- Ogg1 and expressing similar levels of glycosylase were obtained as a gift from Nikolas J. Hodges (University of Birmingham, Birmingham, UK) and were cultured as previously described (22). WT and S326C- Ogg1 stably transfected cells were last authenticated by sequencing, and the OGG1 expression levels in these cells as well as in Ogg1 -/- KO MEFs were tested using anti-OGG1 antibody (Abcam) (31). The WT HA -tagged Ogg1 allele on the pRVY-Tet expression vector was a gift from Joanne Sweasy (Yale University, New Haven, CT).…”

Section: Methodsmentioning

confidence: 99%

Inactivation of a common OGG1 variant by TNF-alpha in mammalian cells

et al. 2015

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Reactive oxygen species threaten genomic integrity by inducing oxidative DNA damage. One common form of oxidative DNA damage is the mutagenic lesion 8-oxoguanine (8-oxodG). One driver of oxidative stress that can induce 8-oxodG is inflammation, which can be initiated by the cytokine tumor necrosis factor alpha (TNF-α). Oxidative DNA damage is primarily repaired by the base excision repair pathway, initiated by glycosylases targeting specific DNA lesions. 8-oxodG is excised by 8-oxoguanine glycosylase 1 (OGG1). A common Ogg1 allelic variant is S326C-Ogg1, prevalent in Asian and Caucasian populations. S326C-Ogg1 is associated with various forms of cancer, and S326C-OGG1 is inactivated by oxidation. However, whether oxidative stress caused by inflammatory cytokines compromises OGG1 variant repair activity remains unknown. We addressed whether TNF-α causes oxidative stress that both induces DNA damage and inactivates S326C-OGG1 via cysteine 326 oxidation. In mouse embryonic fibroblasts, we found that S326C-OGG1 was inactivated only after exposure to H2O2 or TNF-α. Treatment with the antioxidant N-acetylcysteine prior to oxidative stress rescued S326C-OGG1 activity, demonstrated by in vitro and cellular repair assays. In contrast, S326C-OGG1 activity was unaffected by potassium bromate, which induces oxidative DNA damage without causing oxidative stress, and presumably cysteine oxidation. This study reveals that Cys326 is vulnerable to oxidation that inactivates S326C-OGG1. Physiologically relevant levels of TNF-α simultaneously induce 8-oxodG and inactivate S326C-OGG1. These results suggest a mechanism that could contribute to increased risk of cancer among S326C-Ogg1 homozygous individuals.

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Section: Methodsmentioning

confidence: 99%

Inactivation of a common OGG1 variant by TNF-alpha in mammalian cells

et al. 2015

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“…[7][8][9] ROS may be involved in the pathogenesis of bone loss-related diseases. Indeed, decreased plasma antioxidant levels were observed in aged osteoporotic women.…”

Section: Introductionmentioning

confidence: 99%

Titanium dioxide nanoparticles enhance production of superoxide anion and alter the antioxidant system in human osteoblast cells

Niska¹,

Pyszka²,

Tukaj³

et al. 2015

IJN

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Titanium dioxide (TiO 2 ) nanoparticles (NPs) are manufactured worldwide for a variety of engineering and bioengineering applications. TiO 2 NPs are frequently used as a material for orthopedic implants. However, to the best of our knowledge, the biocompatibility of TiO 2 NPs and their effects on osteoblast cells, which are responsible for the growth and remodeling of the human skeleton, have not been thoroughly investigated. In the research reported here, we studied the effects of exposing hFOB 1.19 human osteoblast cells to TiO 2 NPs (5–15 nm) for 24 and 48 hours. Cell viability, alkaline phosphatase (ALP) activity, cellular uptake of NPs, cell morphology, superoxide anion (O 2 •−2 ) generation, superoxide dismutase (SOD) activity and protein level, sirtuin 3 (SIR3) protein level, correlation between manganese (Mn) SOD and SIR, total antioxidant capacity, and malondialdehyde were measured following exposure of hFOB 1.19 cells to TiO 2 NPs. Exposure of hFOB 1.19 cells to TiO 2 NPs resulted in: (1) cellular uptake of NPs; (2) increased cytotoxicity and cell death in a time- and concentration-dependent manner; (3) ultrastructure changes; (4) decreased SOD and ALP activity; (5) decreased protein levels of SOD1, SOD2, and SIR3; (6) decreased total antioxidant capacity; (7) increased O 2 •− generation; and (8) enhanced lipid peroxidation (malondialdehyde level). The linear relationship between the protein level of MnSOD and SIR3 and between O 2 •− content and SIR3 protein level was observed. Importantly, the cytotoxic effects of TiO 2 NPs were attenuated by the pretreatment of hFOB 1.19 cells with SOD, indicating the significant role of O 2 •− in the cell damage and death observed. Thus, decreased expression of SOD leading to increased oxidizing stress may underlie the nanotoxic effects of TiO 2 NPs on human osteoblasts.

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“…Some previous studies have already demonstrated that TiO 2 NPs can absorb metal ions (including Pb, As, Cu, and Cd) and organic compounds (such as BPA and p, p'-DDT) in the solution 27,[37][38][39][40][41] and synergistic effects of TiO 2 NPs with chemicals has been demonstrated in cellular oxidative stress damage and decreased LC 50 among aquatic organisms. One possible mechanism of the antagonistic effects is that glucose can promote the aggregation of TiO 2 NPs.…”

Section: Accepted Manuscriptmentioning

confidence: 97%