Cadmium Exposure Enhances Bisphenol A-Induced Genotoxicity through 8-Oxoguanine-DNA Glycosylase-1 OGG1 Inhibition in NIH3T3 Fibroblast Cells

Abstract

Background: Both cadmium (Cd) and bisphenol A (BPA) are commonly encountered in humans' daily activities, but their combined genotoxic effects remain unclear. Methods: In the present study, we exposed a mouse embryonic fibroblast cell line (NIH3T3) to Cd for 24 h, followed by a 24 h BPA exposure to evaluate toxicity. The cytotoxicity was evaluated by viability with CCK-8 assay and lactate dehydrogenase (LDH) release. Reactive oxygen species (ROS) production was measured by 2′,7′-dichlorofluorescein diacetate (DCFH-DA). And DNA damage was measured by 8-hydroxydeoxyguanosine (8-OHdG), phosphorylated H2AX (γH2AX) and the comet assay. The flow cytometry was used to detect cell cycle distribution, and apoptosis was determined by TUNEL assay and western blot against poly-ADP-ribose polymerase (PARP). Results: The results showed that Cd or BPA treatments alone (with the exception of BPA exposure at 50 μM) did not alter cell viability. However, pre-treatment with Cd aggravated the BPA-induced reduction in cell viability; increased BPA-induced LDH release, ROS production, DNA damage and G2 phase arrest; and elevated BPA-induced TUNEL-positive cells and the expression levels of cleaved PARP. Cd exposure concurrently decreased the expression of 8-oxoguanine-DNA glycosylase-1 (OGG1), whereas OGG1 over-expression abolished the enhancement of Cd on BPA-induced genotoxicity and cytotoxicity. Conclusion: These findings indicate that Cd exposure aggravates BPA-induced genotoxicity and cytotoxicity through OGG1 inhibition.

The effects of different bisphenol derivatives on oxidative stress, DNA damage and DNA repair in RWPE‐1 cells: A comparative study

“…DNA damage for bisphenols was seen in the order of BPS > BPF > BPA. Other researchers have also reported that BPA caused oxidative DNA damage both in vitro (Fic et al, ; Skledar et al, ; Xin et al, ) and in vivo (Chen et al, ; Tiwari et al, ). There are not many studies comparing the genotoxic effects of bisphenol derivatives.…”

“…The researchers concluded that BPA promoted cell survival following oxidative DNA damage after exposure to KBrO 3 . In another study, Chen et al () showed that cadmium exposure aggravated BPA‐induced genotoxicity and cytotoxicity through OGG1 inhibition in mouse embryonic fibroblast cell line (NIH3T3).…”

Ginseng Rh2 protects endometrial cells from oxygen glucose deprivation/re-oxygenation

“…The fluorescent dye DCFH-DA (2′,7′-dichlorofluorescein diacetate) assay was applied to examine cellular ROS level [ 48 – 50 ]. DCFH-DA will be hydrolysed by intracellular esterases to DCF.…”

Ultrastructural, Confocal and Viscoelastic Characteristics of Whole Blood and Plasma After Exposure to Cadmium and Chromium Alone and in Combination: An Ex Vivo Study

“…Cd binds sulfhydryl groups of proteins and glutathione (GSH) and especially GSH depletion results in increased production of reactive oxygen species (ROS) such as hydrogen peroxide, superoxide anion and hydroxyl radical [39-42]. Cr in contrast enters the redox cycle and acts as a catalyst of the Fenton reaction involving H 2 O 2 , leading to an increase in ROS production and alters erythrocyte membrane fluidity and integrity making erythrocytes more fragile and less osmotic resistant [40, 43].…”