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Silencing expression of the catalytic subunit of DNA-dependent protein kinase by small interfering RNA sensitizes human cells for radiation-induced chromosome damage, cell killing, and mutationTargeted gene silencing in mammalian cells by RNA interference (RNAi) using small interfering RNAs (siRNAs) was recently described by Elbashir et al. (S. M. Elbashir et al., Nature (Lond.), 411: 494-498, 2001). We have used this methodology in several human cell strains to reduce expression of the Prkdc (DNA-PKcs) gene coding for the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs) that is involved in the nonhomologous end joining of DNA double-strand breaks. We have also demonstrated a radiosensitization for several phenotypic endpoints of radiation damage. In low-passage normal human fibroblasts, siRNA knock-down of DNA-PKcs resulted in a reduced capacity for restitution of radiation-induced interphase chromosome breaks as measured by premature chromosome condensation, an increased yield of acentric chromosome fragments at the first postirradiation mitosis, and an increased radiosensitivity for cell killing. For three strains of related human lymphoblasts, DNA-PKcs-targeted siRNA transfection resulted in little or no increase in radiosensitivity with respect to cell killing, a 1.5-fold decrease in induced mutant yield in TK6- and p53-null NH32 cells, but about a 2-fold increase in induced mutant yield in p53-mutant WTK1 cells at both the hypoxanthine quanine phosphoribosyl transferase (hprt) and the thymidine kinase loci.
Document ID
20040087989
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Peng, Yuanlin
(Colorado State University Fort Collins Colorado 80523-1681, United States)
Zhang, Qinming
Nagasawa, Hatsumi
Okayasu, Ryuichi
Liber, Howard L.
Bedford, Joel S.
Date Acquired
August 21, 2013
Publication Date
November 15, 2002
Publication Information
Publication: Cancer research
Volume: 62
Issue: 22
ISSN: 0008-5472
Subject Category
Aerospace Medicine
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Discipline Radiation Health

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