Caenorhabditis elegans strain:N2 Raw sequence reads

Per- and polyfluoroalkyl substances (PFAS) are a class of globally ubiquitous persistent organic pollutants (POPs). While three PFAS compounds are presently regulated by the Stockholm Convention to curtail their production and usage, hundreds of others continue to be employed in various commercial products. The reproductive and genotoxic impacts of PFAS have garnered considerable attention; however, their potential mutagenicity on germ cells remains largely unexplored. In this study, we employed a 20-generation mutation accumulation assay coupled with whole-genome sequencing to comprehensively investigate the mutagenic effects of four representative PFAS compounds (perfluorooctanoic acid, perfluorononanoic acid, perfluorodecanoic acid, and perfluorooctanesulfonic acid) at environmentally relevant doses on Caenorhabditis elegans (C. elegans) germ cells. Our findings reveal that while PFNA does not exhibit multigenerational toxicity, it significantly enhances mutation rates, characterized by single-base insertions and deletions (indel), indel events within repetitive DNA sequences, and T:A>C:G substitutions. These results suggest that PFNA may induce mutations by impeding the mismatch repair process. Although the other three PFAS compounds did not show significant mutagenicity, we observed an increase in microhomology-mediated deletions and large deletions in the mutation spectrum of PFOA, indicating a potential role in triggering DNA double-strand breaks (DSB). This study represents the first comprehensive analysis of the genome-wide mutational profile of PFAS compounds. Additionally, our results highlight the importance of assessing medium-chain PFAS for their mutagenic potential.