Clinically relevant radioresistant cells efficiently repair DNA double-strand breaks induced by X-rays

Yoshikazu Kuwahara, Li Li, Taisuke Baba, Hironobu Nakagawa, Tsutomu Shimura, Yoichiro Yamamoto, Yasuhito Ohkubo, Manabu Fukumoto

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Radiotherapy is one of the major therapeutic modalities for eradicating malignant tumors. However, the existence of radioresistant cells remains one of the most critical obstacles in radiotherapy and radiochemotherapy. Standard radiotherapy for tumor treatment consists of approximately 2 Gy once a day, 5 days a week, over a period of 5-8 weeks. To understand the characteristics of radioresistant cells and to develop more effective radiotherapy, we established a novel radioresistant cell line, HepG2-8960-R with clinical relevance from parental HepG2 cells by long-term fractionated exposure to 2 Gy of X-rays. HepG2-8960-R cells continued to proliferate with daily exposure to 2 Gy X-rays for more than 30.days, while all parental HepG2 cells ceased. After exposure to fractionated 2 Gy X-rays, induction frequencies of micronuclei and remaining foci of γ-H2AX in HepG2-8960-R were less than those in HepG2. Flow cytometric analysis revealed that the proportion of cells in S- and G2/M-phase of the cell cycle was higher in HepG2-8960-R than in HepG2. These suggest that the response of clinically relevant radioresistant (CRR) cells to fractionated radiation is not merely an accumulated response to each fractionated radiation. This is the first report on the establishment of a CRR cell line from an isogenic parental cell line.

Original languageEnglish
Pages (from-to)747-752
Number of pages6
JournalCancer science
Volume100
Issue number4
DOIs
Publication statusPublished - 2009 Aug 20

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Kuwahara, Y., Li, L., Baba, T., Nakagawa, H., Shimura, T., Yamamoto, Y., Ohkubo, Y., & Fukumoto, M. (2009). Clinically relevant radioresistant cells efficiently repair DNA double-strand breaks induced by X-rays. Cancer science, 100(4), 747-752. https://doi.org/10.1111/j.1349-7006.2009.01082.x