@misc{oai:repo.qst.go.jp:00069031,
 author = {Sudou, Hitomi and Tsuji, Atsushi and Sugyou, Aya and Sogawa, Chizuru and Saga, Tsuneo and Harada, Yoshinobu and 須藤 仁美 and 辻 厚至 and 須尭 綾 and 曽川 千鶴 and 佐賀 恒夫 and 原田 良信},
 month = {Jul},
 note = {Carcinogenesis is thought to be a multistep process that occurs through the accumulation of mutations in multiple genes required for the maintenance of normal growth control. Genomic instability is considered the earliest cellular event in the process of carcinogenesis. Although genomic instability is induced by ionizing radiation, the molecular mechanisms underlying this process are poorly understood. Cell cycle checkpoints play a key role in cell survival following DNA damage. The failure of DNA repair and cell cycle regulation in response to DNA damage are thought to be important factors in the early stages of genomic instability. Several known genes are reportedly associated not only with DNA damage repair and cell cycle regulation but also with radiation susceptibility. Thus, the identification of novel radiation susceptibility genes will likely help elucidate the molecular mechanisms underlying DNA damage–induced genomic instability.
　By the large-scale expression profiling of 15 human cell lines and three mouse strains having varying degrees of susceptibility to ionizing radiation, we identified 200 genes correlated with radiation susceptibility. We constructed the shRNA library of these 200 genes and screened this library using a 96-well format and measuring the cell survivals, as determined by a sulforhodamine B–based cell proliferation assay, after X-irradiation. We identified 12 genes involved in cellular proliferation after irradiation. Three genes, ATM, ATR and CDKN1A, were known to be radiation susceptibility genes and other nine genes have not been reported to be associated with radiation susceptibility. Eight of the 12 genes were reported to directly or potentially regulate cell cycle, and the remaining four genes have not been reported biological functions. We then performed cell cycle analysis of cells transfected with shRNA vectors against thee four genes following X-irradiation, and found that knockdown cells of one gene did not accumulate at G2/M phase. This result suggests that one gene is associated with G2/M checkpoint after DNA damage. Further study of these 12 genes would help elucidate the molecular mechanism for genomic instability and carcinogenesis, and develop novel drugs for effective tumor radiotherapy and early diagnosis., １３ｔｈ International Congress of Radiation Reserch},
 title = {A Loss of Function Screening for Radiation Susceptibility Genes},
 year = {2007}
}