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

Perfluorooctanesulfonate (PFOS) has been widely detected in the environment, wildlife and humans, but few studies have ever examined its mutagenic effect in vivo. In the present study, we use a transgenic fish model, the λ transgenic medaka, to evaluate the potential mutagenicity of PFOS in vivo following a subchronic exposure of 30 days. The mutant frequency of cII target gene was 3.46 × 10−5 in liver tissue from control fish, which increased by 1.4-fold to 4.86 × 10−5 in fish exposed to 6.7 μg/L PFOS, 1.55-fold to 5.36 × 10−5 in fish exposed to 27.6 μg/L PFOS, and 2.02-fold to 6.99 × 10−5 in fish exposed to 87.6 μg/L PFOS. This dose-dependent increase of mutant frequency was also accompanied with mutational spectrum changes associated with PFOS exposure. In particular, PFOS-induced mutation was characterized by +1 frameshift mutations, which increased from 0% in control fish to 13.2% in fish exposed to 27.6 μg/L PFOS and 14.6% in fish exposed to 87.6 μg/L PFOS. Our findings provide the first evidence of PFOS’s mutagenicity in an aquatic model system. Given the fact that most conventional mutagenic assays were negative for PFOS, we propose that PFOS-induced mutation in liver tissue of λ transgenic medaka may be mediated through compromised liver function.

[1]  Changjiang Huang,et al.  Chronic perfluorooctane sulfonate (PFOS) exposure induces hepatic steatosis in zebrafish. , 2016, Aquatic toxicology.

[2]  T. Hei,et al.  Mutagenic Effects of Perfluorooctanesulfonic Acid in gpt Delta Transgenic System Are Mediated by Hydrogen Peroxide. , 2015, Environmental science & technology.

[3]  D. Knapen,et al.  Toxicity evaluation of perfluorooctane sulfonate (PFOS) in the liver of common carp (Cyprinus carpio). , 2008, Aquatic toxicology.

[4]  Q. Lian,et al.  Perfluorinated chemicals in blood of residents in Wenzhou, China. , 2011, Ecotoxicology and environmental safety.

[5]  K. Yu,et al.  Induction of oxidative stress and apoptosis by PFOS and PFOA in primary cultured hepatocytes of freshwater tilapia (Oreochromis niloticus). , 2007, Aquatic toxicology.

[6]  Kouji Harada,et al.  Perfluorooctanoate and Perfluorooctane Sulfonate Concentrations in Surface Water in Japan , 2004, Journal of occupational health.

[7]  J. M. Keller,et al.  Suppression of humoral immunity in mice following exposure to perfluorooctane sulfonate. , 2008, Toxicological sciences : an official journal of the Society of Toxicology.

[8]  J C Reed,et al.  Somatic Frameshift Mutations in the BAX Gene in Colon Cancers of the Microsatellite Mutator Phenotype , 1997, Science.

[9]  F. Whiteman,et al.  Sub-chronic exposure to 1,1-dichloropropene induces frameshift mutations in λ transgenic medaka , 2006 .

[10]  N. Archer,et al.  Postnatal evaluation , 2018, Fetal Cardiology.

[11]  R. Blust,et al.  Evaluation of the toxicological effects of perfluorooctane sulfonic acid in the common carp (Cyprinus carpio). , 2003, Aquatic toxicology.

[12]  H. Yamamoto,et al.  Frameshift somatic mutations in gastrointestinal cancer of the microsatellite mutator phenotype. , 1997, Cancer research.

[13]  C. Lau,et al.  Exposure to perfluorooctane sulfonate during pregnancy in rat and mouse. I: maternal and prenatal evaluations. , 2003, Toxicological sciences : an official journal of the Society of Toxicology.

[14]  R. Winn,et al.  Transfer, methylation and spontaneous mutation frequency of ΦX174am3cs70 sequences in medaka (Oryzias latipes) and mummichog (Fundulus heteroclitus): Implications for gene transfer and environmental mutagenesis in aquatic species , 1995 .

[15]  D. Keil,et al.  Gestational exposure to perfluorooctane sulfonate suppresses immune function in B6C3F1 mice. , 2008, Toxicological sciences : an official journal of the Society of Toxicology.

[16]  H. Kling,et al.  Antimutagenicity of green tea polyphenols in the liver of transgenic medaka , 2005, Environmental and molecular mutagenesis.

[17]  Jennifer A Field,et al.  Occurrence and persistence of perfluorooctanesulfonate and other perfluorinated surfactants in groundwater at a fire-training area at Wurtsmith Air Force Base, Michigan, USA. , 2003, Journal of environmental monitoring : JEM.

[18]  Takayoshi Suzuki,et al.  In vivo transgenic mutation assays. , 2003, Mutation research.

[19]  K. Kinzler,et al.  Microsatellite instability and mutations of the transforming growth factor beta type II receptor gene in colorectal cancer. , 1995, Cancer research.

[20]  C. Pinkert Transgenic Animal Technology: A Laboratory Handbook , 2014 .

[21]  D. Costopoulou,et al.  Levels of perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) in blood samples from different groups of adults living in Greece. , 2010, Chemosphere.

[22]  G J Carr,et al.  Statistical design and analysis of mutation studies in transgenic mice , 1995, Environmental and molecular mutagenesis.

[23]  Robert C. Wolpert,et al.  A Review of the , 1985 .

[24]  Nobuyoshi Yamashita,et al.  A survey of perfluorooctane sulfonate and related perfluorinated organic compounds in water, fish, birds, and humans from Japan. , 2003, Environmental science & technology.

[25]  M. Stanton,et al.  Exposure to perfluorooctane sulfonate during pregnancy in rat and mouse. II: postnatal evaluation. , 2003, Toxicological sciences : an official journal of the Society of Toxicology.

[26]  K. Yu,et al.  Chronic effects of water-borne PFOS exposure on growth, survival and hepatotoxicity in zebrafish: a partial life-cycle test. , 2009, Chemosphere.

[27]  R. Winn CHAPTER 10 – Production of Transgenic Fish , 2002 .

[28]  R. Dunham,et al.  Production of Transgenic Fish , 2014 .

[29]  Organisation for Economic Cooperation and Development,et al.  Organisation for economic cooperation and development , 1998 .

[30]  Min Sung Kim,et al.  Frameshift mutation of UVRAG, an autophagy-related gene, in gastric carcinomas with microsatellite instability. , 2008, Human pathology.

[31]  B. Glickman,et al.  Conjugated linoleic acid inhibits mutagenesis by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in the prostate of Big Blue rats. , 2003, Mutagenesis.

[32]  K. Brayer,et al.  Detection of mutations in transgenic fish carrying a bacteriophage lambda cII transgene target. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[33]  G. Ankley,et al.  Reproductive and developmental toxicity and bioconcentration of perfluorooctanesulfonate in a partial life‐cycle test with the fathead minnow (Pimephales promelas) , 2005, Environmental toxicology and chemistry.

[34]  T Tsutsui,et al.  Impact of Airborne Perfluorooctane Sulfonate on the Human Body Burden and the Ecological System , 2003, Bulletin of environmental contamination and toxicology.

[35]  G. Leonardi,et al.  Serum Perfluorooctanoate (PFOA) and Perfluorooctane Sulfonate (PFOS) Concentrations and Liver Function Biomarkers in a Population with Elevated PFOA Exposure , 2012, Environmental health perspectives.

[36]  Robert L. Tanguay,et al.  Toxicity, uptake kinetics and behavior assessment in zebrafish embryos following exposure to perfluorooctanesulphonicacid (PFOS). , 2010, Aquatic toxicology.

[37]  Kyungho Choi,et al.  Toxicity of perfluorooctane sulfonic acid and perfluorooctanoic acid on freshwater macroinvertebrates (Daphnia magna and Moina macrocopa) and fish (Oryzias latipes) , 2008, Environmental toxicology and chemistry.

[38]  W. T. Adams,et al.  Computer program for the analysis of mutational spectra: application to p53 mutations. , 1994, Carcinogenesis.

[39]  H. Viberg,et al.  Neonatal exposure to PFOS and PFOA in mice results in changes in proteins which are important for neuronal growth and synaptogenesis in the developing brain. , 2009, Toxicological sciences : an official journal of the Society of Toxicology.

[40]  R. Winn Trangenic fish as models in environmental toxicology. , 2001, ILAR journal.

[41]  J. Giesy,et al.  Global distribution of perfluorooctane sulfonate in wildlife. , 2001, Environmental science & technology.

[42]  Jiangfei Chen,et al.  Chronic perfluorooctanesulfonic acid exposure disrupts lipid metabolism in zebrafish , 2017, Human & experimental toxicology.

[43]  Derek C G Muir,et al.  Biological monitoring of polyfluoroalkyl substances: A review. , 2006, Environmental science & technology.

[44]  K. Brayer,et al.  Bacteriophage λ and Plasmid pUR288 Transgenic Fish Models for Detecting In Vivo Mutations , 2001, Marine Biotechnology.

[45]  J. S. Eldridge,et al.  Quantitative characterization of trace levels of PFOS and PFOA in the Tennessee River. , 2002, Environmental science & technology.

[46]  Sac-fry Stages,et al.  OECD GUIDELINE FOR TESTING OF CHEMICALS , 2002 .

[47]  J. Domingo,et al.  Exposure of pregnant rats to uranium and restraint stress: effects on postnatal development and behavior of the offspring. , 2006, Toxicology.

[48]  Bingsheng Zhou,et al.  Developmental toxicity and alteration of gene expression in zebrafish embryos exposed to PFOS. , 2008, Toxicology and applied pharmacology.

[49]  T. Glenn,et al.  Transgenic λ medaka as a new model for germ cell mutagenesis , 2008, Environmental and molecular mutagenesis.

[50]  J. Domingo,et al.  Concurrent exposure to perfluorooctane sulfonate and restraint stress during pregnancy in mice: effects on postnatal development and behavior of the offspring. , 2007, Toxicological sciences : an official journal of the Society of Toxicology.