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Record 1 of 4973
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 mutation
Author and Affiliation:
Peng, Yuanlin(Colorado State University Fort Collins, Department of Environmental and Radiological Health Sciences, Colorado 80523-1681, United States)
Zhang, Qinming
Nagasawa, Hatsumi
Okayasu, Ryuichi
Liber, Howard L.
Bedford, Joel S.
Abstract: Targeted 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.
Publication Date: Nov 15, 2002
Document ID:
20040087989
(Acquired Sep 07, 2004)
Subject Category: AEROSPACE MEDICINE
Document Type: Journal Article
Publication Information: Cancer research (ISSN 0008-5472); Volume 62; 22; 6400-4
Publisher Information: United States
Description: In English
Distribution Limits: Unclassified; Publicly available; Unlimited
Rights: Copyright
NASA Terms: CHROMOSOME ABERRATIONS; CHROMOSOMES; DEOXYRIBONUCLEIC ACID; GENE EXPRESSION REGULATION; MUTATIONS; PROTEINS; RADIATION DAMAGE; RADIATION TOLERANCE; RIBONUCLEIC ACIDS; BIOSYNTHESIS; CATALYSIS; CULTURED CELLS; CYTOLOGY; ENZYMOLOGY; FIBROBLASTS; LYMPHOCYTES; MUTAGENESIS; RADIATION EFFECTS
Other Descriptors: CHROMOSOME ABERRATIONS/RADIATION EFFECTS; GENE SILENCING; PROTEIN-SERINE-THREONINE KINASES/ANTAGONISTS & INHIBITORS/BIOSYNTHESIS/GENETICS; RNA, SMALL INTERFERING/GENETICS; RADIATION TOLERANCE/GENETICS; CATALYSIS; CELL DEATH/RADIATION EFFECTS; CELLS, CULTURED; FIBROBLASTS/CYTOLOGY/ENZYMOLOGY/RADIATION EFFECTS; HUMAN; LYMPHOCYTES/CYTOLOGY/ENZYMOLOGY/RADIATION EFFECTS; MUTAGENESIS/RADIATION EFFECTS; TRANSFECTION; NASA DISCIPLINE RADIATION HEALTH; NON-NASA CENTER
Availability Source: Other Sources
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