PFOS-induced apoptosis through mitochondrion-dependent pathway in human–hamster hybrid cells

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 (A L ) cells and mtDNA-depleted (ρ 0 A L ) cells were exposed to PFOS, and assayed for cytotoxicity, mutagenicity, and apoptosis (caspase-3/7, caspase-9 activities). Our results showed that PFOS decreased cell viability in a time- and concentration-dependent manner in A L cells, but not in ρ 0 A L cells. However, long-term exposure to PFOS failed to induce the mutagenic effects at the CD59 locus in A L cells. Exposure to 200 μM PFOS significantly increased the activities of caspase-3/7 and caspase-9 in A L cells, but the activities of these caspases were not affected in ρ 0 A L cells. In addition, PFOS increased the levels of reactive oxygen species (ROS), superoxide anion (O 2 − ), as well as nitric oxide (NO), and decreased mitochondrial membrane potential (MMP) at the concentrations of 100 and 200 μM in A L cells. On the other hand, exposure to PFOS had no effect on intracellular ROS, O 2 − , and NO production in ρ 0 A L cells. Caspase-3/7 activity, which was increased by 200 μM PFOS, could be suppressed by ROS/O 2 − scavengers and nitric oxide synthases (NOSs) inhibitors in A L cells. These results implicate that PFOS-induced apoptosis and oxidative stress is mediated by a mitochondrion-dependent pathway and that the induction of apoptosis might be a protective function against mutagenesis in A L cells exposed to PFOS.