Impacts of two perfluorinated compounds (PFOS and PFOA) on human hepatoma cells: Cytotoxicity but no genotoxicity?

DESP, Nancy Université - Faculté de Médecine de Nancy, 9 Avenue de la forêt de Haye BP 184, 54 505 Vandœuvre-lès-Nancy cedex, France.
International journal of hygiene and environmental health (Impact Factor: 3.83). 06/2011; 214(6):493-9. DOI: 10.1016/j.ijheh.2011.05.010
Source: PubMed


Perfluorinated compounds (PFCs) and particularly two of them, perfluoroctanoate (PFOA) and perfluorooctanesulfonate (PFOS), have been widely produced and used since 1950. They both persist in the environment and accumulate in wildlife and humans. The toxicity of PFOS and PFOA has been studied extensively in rodents with several adverse effects mainly a hepatocarcinogenic potential. Carcinogenic effects are not highlighted in humans' studies. In this study, we investigated the cytotoxic and genotoxic effects of PFOA and PFOS using human HepG2 cells after 1 or 24h of exposure. The cytotoxic and genotoxic potential was evaluated by MTT assay, single cell gel electrophoresis (SCGE) assay and micronucleus assay respectively. We measured the intracellular generation of reactive oxygen species (ROS) using dichlorofluorescein diacetate to identify a potential mechanism of toxicity. We observed a cytotoxic effect of PFOA and PFOS after 24h of exposure starting from a concentration of 200 μM (MTT: -14.6%) and 300 μM (MTT: -51.2%) respectively. We did not observe an increase of DNA damage with the comet assay or micronucleus with the micronucleus assay after exposure to the two PFCs. After 24h of exposure, both PFOA and PFOS highlight a decrease of ROS generation (-5.9% to -23%). We did not find an effect after an hour of exposure. Our findings show that PFOA and PFOS exert a cytotoxic effect on the human cells line HepG2 but nor PFOA or PFOS could induce an increase of DNA damage (DNA strand breaks and micronucleus) or reactive oxygen species at the range concentration tested. Our results do not support that oxidative stress and DNA damage are relevant for potential adverse effects of PFOA and PFOS. These results tend to support epidemiological studies that do not show evidence of carcinogenicity.

37 Reads
  • Source
    • "Perfluorooctane sulfonate (PFOS) 1763-23-1 Equivocal Unknown (Eriksen et al., 2010; Florentin et al., 2011; Jacquet et al., 2012) "

  • Source
    • "General toxicological findings associated with exposure to PFOS and PFOA include hepatotoxicity (Malinverno et al., 2005), hepatomegaly (Elcombe et al., 2012), hepatocellular adenoma (Butenhoff et al., 2012), peroxisomal proliferation (Berthiaume and Wallace, 2002), congestion and thickened epithelial walls in lungs (Cui et al., 2009), reproductive toxicity (Luebker et al., 2005), immunotoxicity (Peden-Adams et al., 2008; Keil et al., 2008; Hu et al., 2010; Fair et al., 2011; Grandjean et al., 2012), and neurotoxicity (Johansson et al., 2008; Mariussen, 2012). In vitro studies show that PFOS and PFOA exert cytotoxic effects on hepatoma HepG2 cells (Florentin et al., 2011). These compounds also exhibit capacity to interfere with the hepatic enzyme activity (Narimatsu et al., 2011) and to exert anti-inflammatory effects modulating the secretion of pro-inflammatory cytokines in blood cells (Brieger et al., 2011; Corsini et al., 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA) are the most notable members of an emerging class of persistent organic pollutants (POPs), poly- and perfluoroalkyl acids (PFASs). In this study, the CCD-18Co myofibroblasts were selected as a cell model to investigate the cytotoxic effects of PFOS and PFOA. The aim was to perform an in vitro evaluation of the ability of these compounds to induce cytotoxicity and modulate mechanisms associated with inflammation as measured by (i) colon fibroblasts viability, (ii) colon fibroblasts proliferation, and (iii) IL-6 production. The data provided in this study suggest that PFOS and PFOA can have cytotoxic potential and modulate processes associated with intestinal inflammation such as myofibroblasts proliferation and IL-6 production at concentrations similar to those detected in vivo. Our results also highlight the influence of culture serum concentration in cytotoxic in vitro studies, which should be considered in future toxicity studies involving PFOS and PFOA. The results contribute to a better knowledge of the effects of PFOS and PFOA in human cells, a phenomenon still not fully examined. Copyright © 2015. Published by Elsevier Ltd.
    Toxicology in Vitro 07/2015; 29(7). DOI:10.1016/j.tiv.2015.07.001 · 2.90 Impact Factor
  • Source
    • "Conversely, irradiation or drugs, which result in DNA damage in some cells, can also induce apoptotic death through a p53-dependent pathway [37] [38]. So far, studies regarding the mutagenicity and carcinogenicity of PFOS are quite conflicting [9] [39] [40]. Using the sensitive A L cell system, we reported previously that 16 days of PFOA exposure had the mutagenic effect on A L cells [26]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Perfluorooctane sulfonate (PFOS) was listed as one of the persistent organic pollutants (POPs) in Stockholm Convention in 2009. Recent evidence showed that PFOS could induce apoptosis both in vivo and in vitro. However, the apoptotic mechanisms induced by PFOS as well as the possible relationship between apoptosis and other PFOS-induced endpoints, remain unclear. In the present study, normal human-hamster hybrid (AL) cells and mtDNA-depleted (ρ(0) AL) cells were exposed to PFOS, and assayed for cytotoxicity, mutagenicity, and apoptosis (caspase-3/7, -9 activities). Our results showed that PFOS decreased cell viability in a time- and concentration-dependent manner in AL cells, but not in ρ(0) AL cells. However, long-term exposure to PFOS failed to induce the mutagenic effects at the CD59 locus in AL cells. Exposure to 200 (M PFOS significantly increased the activities of caspase-3/7 and caspase-9 in AL cells, but the activities of these caspases were not affected in ρ(0) AL cells. In addition, PFOS increased the levels of reactive oxygen species (ROS), superoxide anion (O2(.-)), as well as nitric oxide (NO), and decreased mitochondrial membrane potential (MMP) at the concentrations of 100 and 200μM in AL cells. On the other hand, exposure to PFOS had no effect on intracellular ROS, O2(.-), and NO production in ρ(0) AL cells. Caspase-3/7 activity, which was increased by 200 (M PFOS, could be suppressed by ROS/O2(.-) scavengers and nitric oxide synthases (NOSs) inhibitors in AL cells. These results implicate that PFOS-induced apoptosis and oxidative stress is mediated by a mitochondria-dependent pathway and that the induction of apoptosis might be a protective function against mutagenesis in AL cells exposed to PFOS.
    Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 04/2013; 754(1-2). DOI:10.1016/j.mrgentox.2013.04.004 · 3.68 Impact Factor
Show more

Similar Publications