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

Yuanhong Chen,Michelle B Norris,Qiaoxiang Dong,Wei Hu,Changjiang Huang,Richard Winn,Chenglian Bai,Dongren Yang,Jiangfei Chen,Qihao Wei,Shushan Hua

doi:10.1038/srep38466

Yuanhong Chen, Michelle B Norris + Show 9 more

Open Access

https://doi.org/10.1038/srep38466

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Abstract

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.

Highlights

Perfluorinated chemicals (PFCs) are widely used in surfactants, lubricants, polymers, and firefighting foams[1]
Our findings showed that PFOS exhibited weak mutagenic effect in vivo, and the PFOS-induced mutational spectrum was characterized by +1 frameshift mutations
The mean mutant frequency of control fish was 3.46 × 10−5 (n = 7), which is similar to the spontaneous mutant frequency of (4.3 ± 0.6) × 10−5 observed previously in the liver tissue of λtransgenic medaka[23]

Summary

Introduction

Perfluorinated chemicals (PFCs) are widely used in surfactants, lubricants, polymers, and firefighting foams[1]. The λtransgenic medaka, a transgenic fish model for in vivo mutation analysis, carries multiple copies of the λbacteriophage vector that harbors the cII gene as a mutant target[23]. Earlier studies have shown that cII transgene is a reliable and sensitive mutation target that meets the fundamental requirements of mutation analysis[27,29,30]. We use this λtransgenic medaka to assess the mutagenic effect of PFOS in vivo. We exposed the λtransgenic medaka to various concentrations of PFOS for 30 days and the induction of cII mutations in the liver tissues were assessed. Our findings showed that PFOS exhibited weak mutagenic effect in vivo, and the PFOS-induced mutational spectrum was characterized by +1 frameshift mutations

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Results

Conclusion