Reduced Tumorigenicity of Mouse ES Cells and the Augmented Anti-Tumor Therapeutic Effects under Parg Deficiency

PolyADP-ribosylation is a post-translational modification of proteins, and poly(ADP-ribose) (PAR) polymerase (PARP) family proteins synthesize PAR using NAD as a substrate. Poly(ADP-ribose) glycohydrolase (PARG) functions as the main enzyme for the degradation of PAR. In this study, we investigated the effects of deficiency on tumorigenesis and therapeutic efficacy of DNA damaging agents, using mouse ES cell-derived tumor models. To examine the effects of deficiency on tumorigenesis, and ES cells were subcutaneously injected into nude mice. The results showed that deficiency delays early onset of tumorigenesis from ES cells. All the tumors were phenotypically similar to teratocarcinoma and microscopic findings indicated that differentiation spectrum was similar between the genotypes. The augmented anti-tumor therapeutic effects of X-irradiation were observed under deficiency. These results suggest that deficiency suppresses early stages of tumorigenesis and that inhibition, in combination with DNA damaging agents, may efficiently control tumor growth in particular types of germ cell tumors.