Whole-genome gene expression profiling reveals the major role of nitric oxide in mediating the cellular transcriptional response to ionizing radiation in normal human fibroblasts.
The indirect biological effects of ionizing radiation (IR) are thought to be mediated largely by reactive oxygen and nitrogen species (ROS and RNS). However, no data are available on how nitric oxide (NO) modulates the response of normal human cells to IR exposures at the level of the whole transcriptome. Here, we examined the effects of NO and ROS scavengers, carboxy-PTIO and DMSO, on changes in global gene expression in cultured normal human fibroblasts after exposures to gamma-rays, aiming to elucidate the involvement of ROS and RNS in transcriptional response to IR. We found that NO depletion dramatically affects the gene expression in normal human cells following irradiation with gamma-rays. We observed striking (more than seven-fold) reduction of the number of upregulated genes upon NO scavenging compared to reference irradiated cell cultures. NO scavenging in irradiated IMR-90 cells results in induction of p53 signaling, DNA damage and DNA repair pathways.
Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. sokolovm@mail.nih.gov
Mykyta V
MV
Sokolov
Igor G
IG
Panyutin
Ronald D
RD
Neumann
D001565:Benzoates; D002460:Cell Line; D004121:Dimethyl Sulfoxide; D005347:Fibroblasts; D016166:Free Radical Scavengers / Q000378:metabolism*; D005720:Gamma Rays; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000528:radiation effects*; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D007093:Imidazoles; D009569:Nitric Oxide / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D014158:Transcription, Genetic / Q000502:physiology / Q000528:radiation effects*
D001565:Benzoates; D016166:Free Radical Scavengers; D007093:Imidazoles; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D009569:Nitric Oxide; D004121:Dimethyl Sulfoxide