title: 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.
authors: †Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences and Anhui Province, Hefei, Anhui 230031, P. R. China.
authors: Yichen
authors: Y
authors: Wang
authors: ‡Jiangsu Tripod Preclinical Research Laboratories, Pukou Economic Development Zone, 9# Xinglong Road, Nanjing, China.
authors: Xuefeng
authors: X
authors: Zhang
authors: †Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences and Anhui Province, Hefei, Anhui 230031, P. R. China.
authors: Meimei
authors: M
authors: Wang
authors: §Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and Faculty of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P. R. China.
authors: Yiyi
authors: Y
authors: Cao
authors: †Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences and Anhui Province, Hefei, Anhui 230031, P. R. China.
authors: Xinan
authors: X
authors: Wang
authors: †Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences and Anhui Province, Hefei, Anhui 230031, P. R. China.
authors: Yun
authors: Y
authors: Liu
authors: †Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences and Anhui Province, Hefei, Anhui 230031, P. R. China.
authors: Juan
authors: J
authors: Wang
authors: ‡Jiangsu Tripod Preclinical Research Laboratories, Pukou Economic Development Zone, 9# Xinglong Road, Nanjing, China.
authors: Jing
authors: J
authors: Wang
authors: †Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences and Anhui Province, Hefei, Anhui 230031, P. R. China.
authors: Lijun
authors: L
authors: Wu
authors: ∥Center for Radiological Research, Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, New York City, New York 10027, United States.
authors: Tom K
authors: TK
authors: Hei
authors: §Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and Faculty of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P. R. China.
authors: Yang
authors: Y
authors: Luan
authors: †Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences and Anhui Province, Hefei, Anhui 230031, P. R. China.
authors: An
authors: A
authors: Xu
mesh_terms: D017738:Alkanesulfonic Acids / Q000633:toxicity*; D000818:Animals; D004249:DNA Damage / Q000187:drug effects*; D005466:Fluorocarbons / Q000633:toxicity*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009152:Mutagenicity Tests
chemical_list: D017738:Alkanesulfonic Acids; D005466:Fluorocarbons; C076994:perfluorooctane sulfonic acid; D006861:Hydrogen Peroxide