Radiosensitization by hyperthermia in the chicken B-lymphocyte cell line DT40 and its derivatives lacking nonhomologous end joining and/or homologous recombination pathways of DNA double-strand break repair

Hong Lan Yin, Yuka Suzuki, Yoshihisa Matsumoto, Masanori Tomita, Yoshiya Furusawa, Atsushi Enomoto, Akinori Morita, Mizuho Aoki, Fumio Yatagai, Takahiko Suzuki, Yoshio Hosoi, Kuni Ohtomo, Norio Suzuki

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Hyperthermia has a radiosensitizing effect, which is one of the most important biological bases for its use in cancer therapy with radiation. Although the mechanism of this effect has not been clarified in molecular terms, possible involvement of either one or both of two major DNA double-strand break (DSB) repair pathways, i.e. nonhomologous end joining (NHEJ) and homologous recombination (HR), has been speculated. To test this possibility, we examined cells of the chicken B-lymphocyte cell line DT40 and its derivatives lacking NHEJ and/or HR: KU701/1, DNA-PKcs-/-/-, RAD54 -/- and KU70-/-/RAD54-/- Radiosensitization by hyperthermia could be seen in all of the mutants, including KU70 -/-/RAD54-/- which lacked both NHEJ and HR. Therefore, radiosensitization by hyperthermia cannot be explained simply by its inhibitory effects, if any, on NHEJ and/or HR alone. However, in NHEJ-defective KU70 -/- and DNA-PKcs-/-/-, consisting of two subpopulations with distinct radiosensitivity, the radio-sensitive subpopulation, which is considered to be cells in G1 and early S, was not sensitized. Substantial sensitization was seen only in the radioresistant subpopulation, which is considered to be cells in late S and G2, capable of repairing DSBs through HR. This observation did not exclude possible involvement of NHEJ in G1 and early S phase and also suggested inhibitory effects of hyperthermia on HR. Thus partial contribution of NHEJ and HR in radiosensitization by hyperthermia, especially that depending on the cell cycle stage, remains to be Considered.

Original languageEnglish
Pages (from-to)433-441
Number of pages9
JournalRadiation Research
Volume162
Issue number4
DOIs
Publication statusPublished - 2004 Oct
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging

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