A Caenorhabditis elegans tissue model of radiation-induced reproductive cell death

Abstract

We have developed a tissue model of radiation-induced reproductive cell death in the nematode Caenorhabditis elegans. Reproductive cell death is the primary mode of death in tissue multipotential precursor cells, or "clonogens," the targets of cytotoxic therapy, whose elimination results in normal tissue damage as well as solid-tumor eradication. Through extensive morphologic and genetic analysis, we have confirmed that cell death in this model represents reproductive cell death in isolation from apoptotic cell death, affording the opportunity to define the genetic pathways required for protection from reproductive cell death. We have additionally found that the DNA damage response pathway is necessary for protection from reproductive cell death, supporting the long-held tenet that DNA damage is the cause of reproductive cell death and further validating this model. This genetic tissue model provides a valuable tool for oncology-based research and affords a platform to broaden our insight into responses to cytotoxic therapy in tissues.