No Relationship between Subchronic Fluoride Intake and DNA Damage in Wistar Rats

Ribeiro, Daniel Araki; Marques, Mea; Assis, Gérson Francisco de; Anzai, Andrea; Poleti, M. L.; Salvadori, Daisy Maria Fávero

doi:10.1159/000080590

Cited by 27 publications

(16 citation statements)

References 40 publications

(28 reference statements)

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“…Our results clearly demonstrated that fluoride at all concentrations tested did not contribute to the damage of DNA. Our results are consistent with other studies [Li et al, 1987;Ribeiro et al, 2004a]. On the other hand, some researchers reported that fluoride inhibits both protein and DNA synthesis and induces DNA lesions through apoptosis in cultured mammalian cells [Wang et al, 2004;Kubota et al, 2005;Satoh et al, 2005].…”

Section: Discussionsupporting

confidence: 93%

Lack of Effect of Prior Treatment with Fluoride on Genotoxicity of Two Chemical Agents in vitro

Ribeiro

Marques²,

Salvadori³

2007

Caries Res

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The goal of this study was to investigate the ability of fluoride to modulate the genotoxic effects induced by the oxidative agent hydrogen peroxide (H₂O₂) and the alkylating agent methyl methanesulfonate (MMS) in vitro by the single-cell gel (comet) assay. Chinese hamster ovary cells were exposed in culture for 1 h at 37°C to sodium fluoride at 7–100 µg/ml. NaF-treated and control cells were then incubated with 0–10 µM MMS in phosphate-buffered saline (PBS) for 15 min at 37°C, or 0–100 µM H₂O₂ in distilled water for 5 min on ice. Negative control cells were treated with PBS for 1 h at 37°C. Clear concentration-related effects were observed for the two genotoxins. Increase of DNA damage induced by either MMS or H₂O₂was not significantly altered by pretreatment with NaF. The data indicate that NaF does not modulate alkylation-induced genotoxicity or oxidative DNA damage as measured by the single-cell gel (comet) assay.

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Section: Discussionsupporting

confidence: 93%

Lack of Effect of Prior Treatment with Fluoride on Genotoxicity of Two Chemical Agents in vitro

Ribeiro

Marques²,

Salvadori³

2007

Caries Res

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“…Moreover, current literature about the genotoxic potential of fluoride in various cells and/or tissues is contradictory. Studies have shown that fluoride does not induce DNA damage [53–55], whereas other studies have observed fluoride-induced DNA damage in rat and human cells [52,56,57]. The possible mechanisms of fluoride-induced DNA damage are that (1) fluoride directly attacks the free amine groups present in DNA or (2) fluoride acts indirectly through free radicals to create DNA adducts at hydrogen bonds [58].…”

Section: Discussionmentioning

confidence: 99%

Fluoride induces oxidative damage and SIRT1/autophagy through ROS-mediated JNK signaling

Suzuki¹,

Bandoski²,

Bartlett³

2015

Free Radical Biology and Medicine

191

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Fluoride is an effective caries prophylactic, but at high doses can also be an environmental health hazard. Acute or chronic exposure to high fluoride doses can result in dental enamel and skeletal and soft tissue fluorosis. Dental fluorosis is manifested as mottled, discolored, porous enamel that is susceptible to dental caries. Fluoride induces cell stress, including endoplasmic reticulum stress and oxidative stress, which leads to impairment of ameloblasts responsible for dental enamel formation. Recently we reported that fluoride activates SIRT1 and autophagy as an adaptive response to protect cells from stress. However, it still remains unclear how SIRT1/autophagy is regulated in dental fluorosis. In this study, we demonstrate that fluoride exposure generates reactive oxygen species (ROS) and the resulting oxidative damage is counteracted by SIRT1/autophagy induction through c-Jun N-terminal kinase (JNK) signaling in ameloblasts. In the mouse-ameloblast-derived cell line LS8, fluoride induced ROS, mitochondrial damage including cytochrome-c release, up-regulation of UCP2, attenuation of ATP synthesis, and H2AX phosphorylation (γH2AX), which is a marker of DNA damage. We evaluated the effects of the ROS inhibitor N-acetylcysteine (NAC) and the JNK inhibitor SP600125 on fluoride-induced SIRT1/autophagy activation. NAC decreased fluoride-induced ROS generation and attenuated JNK and c-Jun phosphorylation. NAC decreased SIRT1 phosphorylation and formation of the autophagy marker LC3II, which resulted in an increase in the apoptosis mediators γH2AX and cleaved/activated caspase-3. SP600125 attenuated fluoride-induced SIRT1 phosphorylation, indicating that fluoride activates SIRT1/autophagy via the ROS-mediated JNK pathway. In enamel organs from rats or mice treated with 50, 100, or 125 ppm fluoride for 6 weeks, cytochrome-c release and the DNA damage markers 8-oxoguanine, p-ATM, and γH2AX were increased compared to those in controls (0 ppm fluoride). These results suggest that fluoride-induced ROS generation causes mitochondrial damage and DNA damage, which may lead to impairment of ameloblast function. To counteract this impairment, SIRT1/autophagy is induced via JNK signaling to protect cells/ameloblasts from fluoride-induced oxidative damage that may cause dental fluorosis.

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“…It is generally accepted correlation between genotoxic and carcinogenic effects of a variety of chemicals (18). Whether the DNA damage is repaired or persists is important to the fate of cells targeted by chemical carcinogens (33).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of genetic damage in human peripheral lymphocytes exposed to mineral trioxide aggregate and Portland cements

Braz

Camargo

Salvadori

et al. 2006

J of Oral Rehabilitation

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summary Mineral trioxide aggregate (MTA) and Portland cement are being used in dentistry as root-end-filling material for periapical surgery and for the sealing of communications between the root canal system and the surrounding tissues. However, genotoxicity tests for complete risk assessment of these compounds have not been conducted up to now. In the present study, the genotoxic effects of MTA and Portland cements were evaluated in peripheral lymphocytes from 10 volunteers by the alkaline single cell gel (comet) assay. The results pointed out that the single cell gel (comet) assay failed to detect the presence of DNA damage after a treatment of peripheral lymphocytes by MTA and Portland cements for concentrations up to 1000 mug mL(-1). In summary, our results indicate that exposure to MTA or Portland cements may not be a factor that increases the level of DNA lesions in human peripheral lymphocytes as detected by single cell gel (comet) assay.

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No Relationship between Subchronic Fluoride Intake and DNA Damage in Wistar Rats

Cited by 27 publications

References 40 publications

Lack of Effect of Prior Treatment with Fluoride on Genotoxicity of Two Chemical Agents in vitro

Lack of Effect of Prior Treatment with Fluoride on Genotoxicity of Two Chemical Agents in vitro

Fluoride induces oxidative damage and SIRT1/autophagy through ROS-mediated JNK signaling

Evaluation of genetic damage in human peripheral lymphocytes exposed to mineral trioxide aggregate and Portland cements

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