Whole-genome sequencing reveals germ cell mutagenicity of alpha-endosulfan in Caenorhabditis elegans

Endosulfan is an extensively used organochlorine pesticide around the world, which was classified as persistent organic pollutants (POPs) in 2009. Although previous studies have documented the reproductive toxicity of endosulfan in a variety of organisms, little is known about the influence of endosulfan on genome stability of germ cells and non-exposed progeny. Here we applied whole genome sequencing to explore the germ cell mutagenicity of alpha-endosulfan in Caenorhabditis elegans (C. elegans). We found that, although low doses of alpha-endosulfan exhibited minimal minor effect on reproductive capacity of C. elegans, chronic exposure to 1 uM alpha-endosulfan significantly increased the mutation frequencies of non-exposed progeny. Further analysis of genome-wide mutation spectra demonstrated that alpha-endosulfan preferentially elicited A:T->G:C substitutions and clustered mutations. By using worms deficient in DNA damage response genes, our results suggest the involvement of translesion synthesis polymerase eta in modulating alpha-endosulfan-induced mutations in germ cells. Together, these observations reveal the germ cell mutagenicity of alpha-endosulfan in C. elegans, and the possible underlying mechanism. In addition, our findings implicate that germ cell mutagenicity might be a necessary consideration for the health risk assessment of environmental chemicals such as POPs.