Mutagenic Effects of Perfluorooctanesulfonic Acid in gpt Delta Transgenic System Are Mediated by Hydrogen Peroxide

Abstract

Perfluorooctane sulfate (PFOS), a persistent organic pollutant, has recently been closely linked with an increased risk of tumorigenesis. However, PFOS has yielded negative results in various tests of genotoxicity. The present study aimed to investigate the mutagenic response to PFOS in the gpt delta transgenic mouse mutation system and to illustrate the contribution of hydrogen peroxide (H2O2) to PFOS genotoxicity. Mutations at the redBA/gam loci were determined by Spi(-) assay both in vitro and in vivo. DNA damage was measured by phosphorylated histone H2AX (γ-H2AX) and mouse bone marrow micronucleus (MN) testing. Our data showed that PFOS induced concentration-dependent increases in γ-H2AX foci and in mutation frequencies at redBA/gam loci in transgenic mouse embryonic fibroblast cells, which were confirmed by the formation of MNs in the bone marrow and the observations of mutation induction in the livers of gpt delta transgenic mice. Concurrent treatment with catalase, an efficient H2O2 scavenger, significantly decreased the formation of γ-H2AX foci and the mutation yields induced by PFOS. In addition, the generation of H2O2 was found to be closely related to the abnormal peroxisomal β-oxidation caused by PFOS. These finding might provide new mechanistical information about genotoxic effects of PFOS.

Risk to human health related to the presence of perfluorooctane sulfonic acid and perfluorooctanoic acid in food

“…PFOS increased mutation frequencies at redBA/gam gene loci in gpt delta transgenic mouse embryonic fibroblasts (Wang et al., ). PFOS failed to induce DNA strand breaks in SHE cells (Jacquet et al., ) and DNA strand breaks or micronuclei in human HepG2 cells (Eriksen et al., ; Florentin et al., ).…”

Effects of Perfluorooctanoic Acid (PFOA) and Perfluorooctane Sulfonic Acid (PFOS) on Soil Microbial Community

“…Qiao, Xie, Zhang, Liu, Xie, Huang and Yu [34] suggested that PFASs would restrict microbial growth and gene expression, such as disrupting immune function and cellular structure. Moreover, the potential biological damage of PFOS include the breaks in the DNA strand, genotoxic effects in cells, and alteration of the permeability of cell membranes [39][40][41]. Notably, few researches have reported the effects of PFASs on the cell membrane.…”

Subchronic perfluorooctanesulfonate (PFOS) exposure induces elevated mutant frequency in an in vivo λ transgenic medaka mutation assay

“…We thus speculate that PFOS-induced mutant frequency in λ transgenic medaka may be mediated through adverse effects on liver tissue or more specifically the lipid oxidation in the liver4243. The very recent study that reported PFOS’s mutagenic effect in vitro also observed increased lipid droplets in cells treated with PFOS and demonstrated that PFOS induced DNA double strand breaks and gene mutation was mediated by H 2 O 2 through abnormal peroxisomal fatty acid β-oxidation41. Similar mechanism may underlie PFOS-induced increase of mutant frequency in the transgenic medaka model system and future studies are necessary to validate this hypothesis.…”

“…PFOS was thus considered as not mutagenic. More recently, a new study reported that PFOS induced concentration-dependent increases in γ-H2AX foci and mutant frequencies at redBA/gam loci in transgenic mouse embryonic fibroblast cells41, suggesting potential genotoxicity of PFOS in vitro . Interestingly, the same study also reported mutation induction, though non-statistically significant, in the livers of gpt delta transgenic mice upon PFOS treatment41, which further supports our finding that PFOS was mutagenic in vivo .…”