title: The modified high-density survival assay is the useful tool to predict the effectiveness of fractionated radiation exposure.
abstract: The high-density survival (HDS) assay was originally elaborated to assess cancer cell responses to therapeutic agents under the influence of intercellular communication. Here, we simplified the original HDS assay and studied its applicability for the detection of cellular radioresistance. We have recently defined clinically relevant radioresistant (CRR) cells, which continue to proliferate with daily exposure to 2 gray (Gy) of X-rays for more than 30 days in vitro. We established human CRR cell lines, HepG2-8960-R from HepG2, and SAS-R1 and -R2 from SAS, respectively. In an attempt to apply the HDS assay to detect radioresistance with clinical relevance, we simplified the original HDS assay by scoring the total number of surviving cells after exposure to X-rays. The modified HDS assay successfully detected radioresistance with clinical relevance. The modified HDS assay detected CRR phenotype, which is not always detectable by clonogenic assay. Therefore, we believe that the modified HDS assay presented in this study is a powerful tool to predict the effectiveness of fractionated radiotherapy against malignant tumors.
authors.affiliation: Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kuwahara
authors.forename: Miyuki
authors.initials: M
authors.lastname: Mori
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Oikawa
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Shimura
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Ohtake
authors.forename: Shiro
authors.initials: S
authors.lastname: Mori
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Ohkubo
authors.forename: Manabu
authors.initials: M
authors.lastname: Fukumoto
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D020014:K562 Cells; D051379:Mice; D008819:Mice, Nude; D008938:Mitosis; D009368:Neoplasm Transplantation; D011836:Radiation Tolerance; D011878:Radiotherapy / Q000379:methods*; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D020298:U937 Cells; D014965:X-Rays
chemical_list: D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue