Radiation-induced gene expression profile of human cells deficient in 8-hydroxy-2'-deoxyguanine glycosylase.

The human OGG1 gene encodes a DNA glycosylase that is involved in the base 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 expression pattern of base excision repair genes and other cellular genes not involved in the base excision pathway in OGG1-deficient human KG-1 cells after ionizing radiation exposure. KG-1 cells have lost OGG1 activity due to a homozygous mutation of Arg229Gln. Gene expression alterations were monitored at 4, 8, 12 and 24 hr in 2 Gy irradiated cells. Large-scale gene expression profiling was assessed with DNA microarray technology. Gene expression analysis identified a number of ionizing radiation-responsive genes, including several novel genes. There were 2 peaks of radiation-induced gene induction or repression: one at 8 hr and the other at 24 hr. Overall the number of downregulated genes was higher than the number of upregulated genes. The highest number of downregulated genes was at 8 hr postirradiation. Genes corresponding to cellular, physiologic, developmental and extracellular processes were identified. The highest number of radiation-induced genes belonged to the signal transduction category, followed by genes involved in transcription and response to stress. Microarray gene expression data were independently validated by relative quantitative RT-PCR. Surprisingly, none of the genes involved in the base excision repair of radiation-induced DNA damage showed altered expression.