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Is level of acetylation directly correlated to radiation sensitivity of cancer cell?

Mutation Research 2018 November 23
It is known that histone deacetylase inhibitors (HDACis) can modify acetylation of tumor cells and affect radiation sensitivity, or, radiosensitivity. While previous studies showed that trichostatin A (TSA, a typical HDACi) could enhance cell acetylation and so be used as radiation-sensitizer in radiotherapy, we questioned if the radiosensitivity is correlated with cellular acetylation directly. So we inspected radiation response of HeLa cells treated with TSA and investigated the time-dependent effect on radiosensitivity. To our surprise, HeLa cells treated with 200 nM TSA for shorter period (6 h) had relatively higher acetylation level but apparently less radiation damage compared to the irradiated cells with same radiation dose treatment of TSA but for longer time (24 h) with lower acetylation level, gainsaying the direct relationship between acetylation and radiosensitivity. We explained that the anti-oxidation activity for the combined treatments with TSA-radiation gave rise to the enhanced radiation protection of the cells at certain period of time. This work has therefore for the first time presented the experimental evidence showing that there is no direct relationship between acetylation and radiation sensitivity, and our results may also provide the guidance for optimized radiotherapy assisted by HDACis in cancer treatment.

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