title: Clinically relevant radioresistant cells efficiently repair DNA double-strand breaks induced by X-rays.
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 gamma-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.
authors.affiliation: Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kuwahara
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Taisuke
authors.initials: T
authors.lastname: Baba
authors.forename: Hironobu
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Shimura
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Ohkubo
authors.forename: Manabu
authors.initials: M
authors.lastname: Fukumoto
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D003114:Colony-Forming Units Assay; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007700:Kinetics; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D011836:Radiation Tolerance / Q000235:genetics*; D014965:X-Rays / Q000009:adverse effects
chemical_list: D004273:DNA, Neoplasm