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Published on: April 28, 2021
Response to multiple radiation doses of fibroblasts over-expressing dominant negative Ku70
Muneyasu Urano1, Yunhong Huang, Fuqiu He
1Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. uranom@mskcc.org
Purpose:
To evaluate the response of cells over-expressing dominant negative (DN) Ku70 to single and multiple small radiation doses.
Methods And Materials:
Clones of fibroblasts over-expressing DNKu70, DNKu70-7, DNKu70-11, and parental Rat-1 cells were irradiated under oxic or hypoxic conditions with single or multiple doses. Cells were trypsinized 0 or 6 h after irradiation to determine surviving fraction (SF).
Results:
Oxic DNKu70-7 or -11 cells trypsinized 6 h after irradiation were 1.52 or 1.25 and 1.28 or 1.15 times more sensitive than oxic Rat-1 at SF of 0.5 and 0.1, respectively. Hypoxic DNKu70-7 or -11 cells trypsinized 6 h after irradiation were 1.44 or 1.70 and 1.33 or 1.51 times more sensitive than hypoxic Rat-1 at SF of 0.5 and 0.1, respectively. To the multiple doses, oxic and hypoxic DNKu70-7 or -11 cells were 1.35 or 1.37 and 2.23 or 4.61 times more sensitive than oxic and hypoxic Rat-1, respectively, resulting in very small oxygen enhancement ratios. Namely, enhancement caused by DNKu70 under hypoxia after multiple doses was greater than that under oxic conditions and greater than that after single dose.
Conclusions:
Over-expression of DNKu70 enhances cells' response to radiation given as a single dose and as multiple small doses. The enhancement after multiple doses was stronger under hypoxic than under oxic conditions. These results encourage the use of DNKu70 fragment in a gene-radiotherapy.
