@article{oai:repo.qst.go.jp:00046557,
 author = {Shirai, Hidenori and Fujimori, Hiroaki and Hirai, Takahisa and Sasai, Keisuke and Okayasu, Ryuichi and Masutani, Mitsuko and et.al and 白井 秀徳 and 平井 崇久 and 笹井 啓資 and 岡安 隆一 and 益谷 美都子},
 issue = {1},
 journal = {Biochemical and Biophysical Research Communications},
 month = {May},
 note = {Poly(ADP-ribose) glycohydrolase (Parg) is the main enzyme involved in poly(ADP-ribose) degradation. Here, the effects of Parg deficiency on sensitivity to low and high linear-energy-transfer (LET) radiation were investigated in mouse embryonic stem (ES) cells. Mouse Parg-/- and poly(ADP-ribose) polymerase-1 deficient (Parp-1-/-) ES cells were used and responses to low and high LET radiation were assessed by clonogenic survival and biochemical and biological analysis methods.
Parg-/-cells were more sensitive to gamma-irradiation than Parp-1-/- cells. Transient accumulation of poly(ADP-ribose) was enhanced in Parg-/-cells. Augmented levels of phosphorylated H2AX (gamma-H2AX)from early phase were observed in Parg-/- ES cells. The induction level of p53 phophorylation at ser18 was similar in wild-type and Parp-1-/- cells and apoptotic cell death process was mainly observed in the both genotypes. These results suggested that the enhanced sensitivity of Parg-/- ES cells to gamma-irradiation involved defective repair of DNA double strand breaks. The effects of Parg and Parp-1 deficiency on the ES cell response to carbon-ion irradiation (LET13 and 70 keV/um) and Fe-ion irradiation (200 keV/um) were also examined. Parg-/- cells were more sensitive to LET 70 keV/um carbon-ion irradiation than Parp-1-/- cells. Enhanced apoptotic cell death also accompanied augmented levels of gamma-H2AX in a biphasic manner peaked at 1 and 24 h. The induction level of p53 phophorylation at
ser18 was not different between wild-type and Parg-/- cells. The augmented level of poly(ADP-ribose) accumulation was noted after carbon-ion irradiation compared to gamma-irradiation even in the wild-type cells. An enhanced poly(ADP-ribose) accumulation was further observed in Parg-/- cells. Both Parg-/- cells and Parp-1-/- cells did not show sensitization to Fe-ion irradiation. Parg deficiency sensitizes mouse ES cells to a wide therapeutic range of LET radiation through the effects on DNA double strand break repair responses and enhanced cell death.},
 pages = {100--106},
 title = {Parg deficiency confers radio-sensitization through enhanced cell death in mouse ES cells exposed to various forms of ionizing radiation},
 volume = {435},
 year = {2013}
}