title: The effect of acute dose charge particle radiation on expression of DNA repair genes in mice.
abstract: The space radiation environment consists of trapped particle radiation, solar particle radiation, and galactic cosmic radiation (GCR), in which protons are the most abundant particle type. During missions to the moon or to Mars, the constant exposure to GCR and occasional exposure to particles emitted from solar particle events (SPE) are major health concerns for astronauts. Therefore, in order to determine health risks during space missions, an understanding of cellular responses to proton exposure is of primary importance. The expression of DNA repair genes in response to ionizing radiation (X-rays and gamma rays) has been studied, but data on DNA repair in response to protons is lacking. Using qPCR analysis, we investigated changes in gene expression induced by positively charged particles (protons) in four categories (0, 0.1, 1.0, and 2.0 Gy) in nine different DNA repair genes isolated from the testes of irradiated mice. DNA repair genes were selected on the basis of their known functions. These genes include ERCC1 (5' incision subunit, DNA strand break repair), ERCC2/NER (opening DNA around the damage, Nucleotide Excision Repair), XRCC1 (5' incision subunit, DNA strand break repair), XRCC3 (DNA break and cross-link repair), XPA (binds damaged DNA in preincision complex), XPC (damage recognition), ATA or ATM (activates checkpoint signaling upon double strand breaks), MLH1 (post-replicative DNA mismatch repair), and PARP1 (base excision repair). Our results demonstrate that ERCC1, PARP1, and XPA genes showed no change at 0.1 Gy radiation, up-regulation at 1.0 Gy radiation (1.09 fold, 7.32 fold, 0.75 fold, respectively), and a remarkable increase in gene expression at 2.0 Gy radiation (4.83 fold, 57.58 fold and 87.58 fold, respectively). Expression of other genes, including ATM and XRCC3, was unchanged at 0.1 and 1.0 Gy radiation but showed up-regulation at 2.0 Gy radiation (2.64 fold and 2.86 fold, respectively). We were unable to detect gene expression for the remaining four genes (XPC, ERCC2, XRCC1, and MLH1) in either the experimental or control animals.
authors.affiliation: Department of Biomolecular Engineering, University of California, Santa Cruz, CA 95064, USA.
authors.forename: Muhammad Akram
authors.initials: MA
authors.lastname: Tariq
authors.forename: Ayodotun
authors.initials: A
authors.lastname: Soedipe
authors.forename: Govindarajan
authors.initials: G
authors.lastname: Ramesh
authors.forename: Honglu
authors.initials: H
authors.lastname: Wu
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shishir
authors.initials: S
authors.lastname: Shishodia
authors.forename: Daila S
authors.initials: DS
authors.lastname: Gridley
authors.forename: Nader
authors.initials: N
authors.lastname: Pourmand
authors.forename: Olufisayo
authors.initials: O
authors.lastname: Jejelowo
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D004720:Endonucleases / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011522:Protons; D011833:Radiation Injuries, Experimental / Q000378:metabolism*; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics; D015854:Up-Regulation; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D011522:Protons; D025521:Tumor Suppressor Proteins; C110901:X-ray repair cross complementing protein 3; D051760:Xeroderma Pigmentosum Group A Protein; C497315:Xpa protein, mouse; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases; D004720:Endonucleases; C499360:Ercc1 protein, mouse