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(PP048) Extreme low dose rate irradiation with heavy ions induces accelerated senescence in primary human cells .
Okayasu, Ryuichi*,1, Okada, Maki1, Okabe, Atsushi1, Uchihori, Yukio1, Suzuki, Masao1, Takahashi, Sentaro, 1 International Space Radiation Lab., Chiba, Chiba-ken, Japan
ABSTRACT- We irradiated normal human fibroblasts (HFL III) with carbon ions (290 MeV/u, LET:70 keV/um) at very low dose (1 mGy total dose) and low dose rate (1 mGy/6 h) and observed the growth kinetics for several months by continuous culturing. The growth of carbon irradiated cells started to slow down much earlier than that of non-irradiated control cells before reaching senescence. In contrast, there was no growth disadvantage in HFL III cells irradiated at the same dose and the dose rate of gamma-rays. The cells irradiated with gamma-rays rather showed a slight delay in the start of senescence. Our theoretical calculations indicate that only one in eighteen cells would be hit by the carbon beams while all the cells were hit by the same dose (rate) of gamma-rays. These data seem to indicate that the accelerated senescence caused by low dose carbon irradiation was a result of by-stander effect. Our measurements of DNA double strand break (DSB) indicator such as gamma-H2AX foci reveal a higher number of foci in carbon irradiated cells than in gamma-irradiated cells at a cell passage near senescence. Taken together, our results suggest that high LET radiation causes different effects than low LET radiation even at very low doses and that the effect of single low dose irradiation can affect the stability of genome many generations after irradiation.
Key words: low dose (rate), high LET, senescence, DNA double strand break
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