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(PP291) Radiation-induced gene expression profile of human cells deficient in 8-hydroxy-2'-deoxyguanine glycosylase.
Chaudhry, Ahmad*,1, 1 Medical Laboratory and Radiation Sciences, Burlington, VT
ABSTRACT- The human OGG1 gene encodes a DNA glycosylase that is involved in the excision repair of 8-hydroxy-2'-deoxyguanine (8-OH-dG) from oxidatively damaged DNA. Cellular 8-OH-dG levels accumulate in the absence of this activity and could be deleterious for the cell. To assess the role of 8-oxoguanine glycosylase (OGG1) in the cellular defense mechanism in a specific DNA repair defect background, we set out to determine the gene expression pattern of base excision repair genes and other cellular genes not involved in base excision pathway in human KG-1 cells featuring a loss of OGG1 activity due to a homozygous mutation of Arg 229 Gln. The KG-1 cells were irradiated with 2 Gy and the gene expression alterations were monitored at 4,8,12 and 24 hours. The large-scale gene expression profiling was assessed with DNA microarray technology. The analysis of microarray data revealed that a number of genes responded to ionizing radiation exposure in KG-1 cells. The gene expression analysis identified a number of novel ionizing radiation responsive genes. There were two peeks of radiation-induced gene induction or repression; one at 8 hours and the other at 24 hours. Overall the number of downregulated genes was higher than the genes that were upregulated. The highest number of downregulated genes was at 8 hours post irradiation. The genes corresponding to cellular, physiological, developmental and extracellular processes were identified. The highest number of radiation-induced genes belongs to signal transduction category followed by genes involved in transcription and response to stress. The microarray gene expression data was independently validated by relative quantitative RT-PCR. Surprisingly none of the genes involved in the base excision repair of radiation-induced DNA damage were found to be altered.
Key words: Microarray, DNA repair
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