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

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 DNA damage and mutation 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 (gamma-H2AX) and mouse bone marrow micronucleus (MN) testing. Our data showed that PFOS ,induced:, concentration-dependent increases in gamma-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 gamma-H2AX foci and the mutation yields induced by PFOS. In addition, the generation of H2O2 was found to be closely related: to the abnormal peroxisoinal, beta-oxidation caused by PFOS. These finding might provide new mechanistical inforination,about genotoxic effects of PFOS.