Mutagenic adaptive response in human lymphoblastoid cells exposed to low and high-LET radiation

DOI
  • VARES Guillaume
    Research Center for Radiation Protection, National Institute of Radiological Sciences
  • WANG Bing
    Research Center for Radiation Protection, National Institute of Radiological Sciences
  • MURAKAMI Masahiro
    Research Center for Radiation Protection, National Institute of Radiological Sciences
  • TANAKA Kaoru
    Research Center for Radiation Protection, National Institute of Radiological Sciences
  • KAKIMOTO Ayana
    Research Center for Radiation Protection, National Institute of Radiological Sciences
  • EGUCHI-KASAI Kiyomi
    Research Center for Radiation Protection, National Institute of Radiological Sciences
  • NENOI Mitsuru
    Research Center for Radiation Protection, National Institute of Radiological Sciences

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Abstract

Exposure to low priming doses of ionizing radiation is known to decrease the biological effects of a subsequent higher challenging dose. This adaptive response (AR) to low dose radiation was described in a variety of models, using various endpoints. In this study, we investigated the ability of low doses of X-rays to induce an AR to the biological effects of high-LET heavy-ion radiation (carbon-ion, neon-ion, 20 to 150 keV/micrometer), in cultured human lymphoblastoid cells TK6 (p53 +/+) and AHH-1 (p53 +/-). We observed that cells adapted by X-rays showed a reduced mutation frequency at HPRT locus after exposure to high-LET radiation at HIMAC (NIRS, Chiba, Japan). AR in our model was dependent on p53 status but linked to neither cell cycle effects nor modulation of radiation-induced apoptosis. The analysis of H2AX phosphorylation kinetics in adapted and non adapted cells suggested that modulation of DNA double-strand break repair activity may be involved in this phenomenon. Knowing that high-LET radiation produces non-randomly distributed DNA damage in the form of clusters, or locally multiply damaged sites (LMDS), it seems that triggering AR by exposing cells to low doses of ionizing radiation could protect cells against the detrimental effects of such damage.

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