The Modified High-Density Survival Assay is the Useful Tool to Predict the Effectiveness of Fractionated Radiation Exposure

  • KUWAHARA Yoshikazu
    Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University
  • MORI Miyuki
    Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University
  • OIKAWA Toshiyuki
    Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University
  • SHIMURA Tsutomu
    Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University
  • OHTAKE Yosuke
    Department of Radiopharmacology, Tohoku Pharmaceutical University
  • MORI Shiro
    Division of Oral and Maxillofacial Surgery, Department of Oro-Maxillofacial Surgical Science, Tohoku University Graduate School of Dentistry
  • OHKUBO Yasuhito
    Department of Radiopharmacology, Tohoku Pharmaceutical University
  • FUKUMOTO Manabu
    Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University

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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.

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