Caenorhabditis elegans Raw sequence reads-Evaluation of chemotherapeutic agent oxaliplatin-induced germ-cell mutagenesis in alternative in vivo model Caenorhabditis elegans
The platinum compound oxaliplatin is a widely used chemotherapeutic drug that shows a broad spectrum of activity in various human tumors. While the treatment-related side effects of oxaliplatin on directly exposed individuals were well-documented, little is known about the influence of oxaliplatin on germ cells and non-exposed progenies. Here we investigated the reproductive toxicity of oxaliplatin in a 3R-compliant in vivo model Caenorhabditis elegans, and evaluated the germ cell mutagenicity of oxaliplatin by using whole genome sequencing. Our results indicated that oxaliplatin treatment significantly disrupts development of spermatids and oocytes. By treating parental worms with oxaliplatin for three successive generations, sequencing data unveiled the clear mutagenic effects of oxaliplatin on germ cells. Analysis of genome-wide mutation spectra showed the preferentially induction of small and large indels by oxaliplatin. In addition, we uncovered the involvement of translesion synthesis polymerase zeta in modulating oxaliplatin-induced mutations in germ cells. These observations suggested that germ cell mutagenicity is worthy of consideration for the health risk assessment of chemotherapeutic drugs.