Response to multiple radiation doses of fibroblasts over-expressing dominant negative Ku70.
OBJECTIVE
To evaluate the response of cells over-expressing dominant negative (DN) Ku70 to single and multiple small radiation doses.


METHODS
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.
Urano
Muneyasu
M
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. uranom@mskcc.org
Huang
Yunhong
Y
He
Fuqiu
F
Minami
Akiko
A
Ling
C Clifton
CC
Li
Gloria C
GC
D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D015687:Cell Hypoxia; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects*; D000072200:Ku Autoantigen; D016014:Linear Models; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000502:physiology*; D051381:Rats; D013997:Time Factors
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D051747:DNA-Activated Protein Kinase; C000606511:Xrcc6 protein, rat; D000072200:Ku Autoantigen