Use of the γH2AX assay for assessing the genotoxicity of bisphenol A and bisphenol F in human cell lines

  title={Use of the $\gamma$H2AX assay for assessing the genotoxicity of bisphenol A and bisphenol F in human cell lines},
  author={Marc Audebert and Laurence Dolo and Elisabeth Perdu and Jean-Pierre Cravedi and Daniel Zalko},
  journal={Archives of Toxicology},
Bisphenol A (BPA) and bisphenol F (BPF) are widely used to manufacture plastics and epoxy resins. Both compounds have been shown to be present in the environment and are food contaminants, with, as a result, a low but chronic exposure of humans. However, the fate and possible bioactivation of these compounds at the level of human cell lines was not completely elucidated yet. In this study, we investigated the ability of human cells (intestinal cell line: LS174T, hepatoma cell line: HepG2, and… 
Evaluation of four human cell lines with distinct biotransformation properties for genotoxic screening.
It is confirmed that the γH2AX ICW assay on HepG2 cells, without an exogenous metabolic activation system, may be a suitable test to predict the in vivo genotoxicity of chemicals with different genotoxic MOA.
Mutagenicity and DNA Damage of Bisphenol a and its Structural Analogues in Hepg2 Cells
None of the tested bisphenols showed a mutagenic effect in Salmonella typhimurium strains TA98 and TA100 in either the presence or absence of external S9-mediated metabolic activation (Aroclor 1254-induced male rat liver).
The cytotoxic and genotoxic effects of bisphenol A on neuronal cells in vitro
In vitro evidence of the potential adverse effects of BPA on the nervous system and possible effects on neuronal development is provided, however, further investigation would be required to decide if environmental concentrations are likely to be potentially hazardous to human health.
Evaluation of genotoxicity using automated detection of γH2AX in metabolically competent HepaRG cells.
It is demonstrated that automated γH2AX detection in metabolically competent HepaRG cells is a suitable high-through put genotoxicity screening assay.
Comparative evaluation of the effects of bisphenol derivatives on oxidative stress parameters in HepG2 cells.
Both of the bisphenol derivatives used as alternatives to BPA also showed similar toxicities and may not be considered as safe alternatives, and Mechanistic studies are needed to elucidate this issue.
Potent Clastogenicity of Bisphenol Compounds in Mammalian Cells-Human CYP1A1 Being a Major Activating Enzyme.
BPs are potently clastogenic in mammalian cells, which require activation primarily by human CYP1A1 and are negatively modulated by phase II metabolism.


Use of the γH2AX assay for assessing the genotoxicity of polycyclic aromatic hydrocarbons in human cell lines.
Biotransformation of genistein and bisphenol A in cell lines used for screening endocrine disruptors.
Genotoxic effects of environmental estrogen-like compounds in CHO-K1 cells.
Biotransformation of bisphenol F by human and rat liver subcellular fractions.
Comparative study of the endocrine-disrupting activity of bisphenol A and 19 related compounds.
The results suggest that the 4-hydroxyl group of the A- phenyl ring and the B-phenyl ring of BPA derivatives are required for these hormonal activities, and substituents at the 3,5-positions of the phenyl rings and the bridging alkyl moiety markedly influence the activities.
Metabolism of bisphenol a in primary cultured hepatocytes from mice, rats, and humans.
The extent of monoglucuronide formation in monolayers of hepatocytes from rats, mice, and humans was determined and when extrapolated to the whole liver, the hepatic capacity for BPA glucuronidation is predicted to be humans > rats > mice.
Pharmacological modulation of genome and proteome alterations in mice treated with the endocrine disruptor bisphenol A.
The in vivo use of proteome analysis proves to be a sensitive tool for the early prediction not only of protective effects but also of adverse effects of chemopreventive agents.
Biotransformations of bisphenol A in a mammalian model: answers and new questions raised by low-dose metabolic fate studies in pregnant CD1 mice.
Data suggest the parental compound is responsible for the estrogenic effects observed in fetuses exposed to BPA during gestation in CD1 pregnant mice in this mammalian model.