title: 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.
  
  
  CONCLUSIONS
  These findings indicate that Cd exposure aggravates BPA-induced genotoxicity and cytotoxicity through OGG1 inhibition.
authors: Department of Occupational Health, Third Military Medical University, Chongqing, People's Republic of China.
authors: Zhi-Yu
authors: ZY
authors: Chen
authors: Chuan
authors: C
authors: Liu
authors: Yong-Hui
authors: YH
authors: Lu
authors: Ling-Ling
authors: LL
authors: Yang
authors: Min
authors: M
authors: Li
authors: Min-Di
authors: MD
authors: He
authors: Chun-Hai
authors: CH
authors: Chen
authors: Lei
authors: L
authors: Zhang
authors: Zheng-Ping
authors: ZP
authors: Yu
authors: Zhou
authors: Z
authors: Zhou
mesh_terms: D000395:Air Pollutants, Occupational / Q000494:pharmacology*; D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D019256:Cadmium Chloride / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage; D045647:DNA Glycosylases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D004338:Drug Combinations; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D005786:Gene Expression Regulation; D006657:Histones / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D010636:Phenols / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000819:agonists / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D000395:Air Pollutants, Occupational; D001559:Benzhydryl Compounds; D019256:Cadmium Chloride; D045647:DNA Glycosylases; D004338:Drug Combinations; D004968:Estrogens, Non-Steroidal; D006657:Histones; D007770:L-Lactate Dehydrogenase; D010636:Phenols; D011065:Poly(ADP-ribose) Polymerases; D017382:Reactive Oxygen Species; C468783:H2AX protein, human; C479058:oxoguanine glycosylase 1, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds