Summary: | The <i>TP53</i> gene is mutated in over 50% of human cancers, and the <i>C. elegans</i><i>p53-1</i><i>(cep-1)</i> gene encodes the ortholog CEP-1. CEP-1 is activated by ultraviolet type C (UVC)-induced DNA damage and activates genes that induce germline apoptosis. UVC treatment of gain-of-function <i>glp-1(ar202gf)/Notch</i> tumorous animals reduces germline stem cell numbers (and overall tumor size), while UVC treatment of double-mutant <i>cep-1/p53(gk138);glp-1/Notch(ar202gf)</i> increases DNA damage adducts and stem cell tumor volume. We compared UVC-induced mitotic stem cell death and animal lifespans for the two different <i>C. elegans</i> tumorous strains. <i>C. elegans</i> stem cell compartment death has never been observed, and we used engulfed small stem cells, notable by green fluorescent puncta, to count cell death events. We found UVC treatment of <i>glp-1(ar202gf)</i> animals increased stem cell death and increased lifespan. However, UVC treatment of double-mutant <i>cep-1/p53(gk138);glp-1/Notch(ar202gf)</i> animals decreased stem cell death, increased tumor volume, and decreased animal lifespan. There are pharmacological agents that induce p53-independent cell death of human cells in culture; and two notable protocols are the PARP-trapping agents of temozolomide plus talazoparib and the nucleoside analogue 8-amino-adenosine. It is important to determine ways to rapidly test for pharmacological agents able to induce p53-independent cell death. We tested feeding <i>cep-1/p53(gk138);glp-1/Notch(ar202gf)</i> nematodes with either 8-amino-adenosine or temozolomide plus talazoparib and found both were able to decrease tumor volume. This is the first comparison for p53-independent responses in <i>cep-1/p53(gk138);glp-1/Notch(ar202gf)</i> animals and showed UVC DNA damage increased tumor volume and decreased lifespan while PARP inhibition decreased tumor volume.
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