title: Poly(ADP-ribose) polymerase activation mediates synchrotron radiation X-ray-induced damage of rodent testes by exacerbating DNA damage and apoptotic changes.
abstract: OBJECTIVE
  Synchrotron radiation (SR) X-ray has great potential for cancer treatment and medical imaging. It is of significance to investigate the mechanisms underlying the effects of SR X-ray irradiation on biological tissues, and search for the strategies for preventing the damaging effects of SR X-ray irradiation on normal tissues. The major aim of our current study is to test our hypothesis that poly(ADP-ribose) polymerase (PARP) plays a significant role in SR X-ray-induced tissue damage.
  
  
  METHODS
  The testes of rodents were pre-treated with PARP inhibitor 3-aminobenzamide (3-AB) or antioxidant N-acetyl-acetylcysteine (NAC), followed by SR X-ray irradiation. PARP activation, double-strand DNA breaks (DSB), Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) signals, caspase-3 activity and weight of the testes were determined.
  
  
  RESULTS
  SR X-ray irradiation produced dose-dependent increases in poly(ADP-ribose) (PAR) formation - an index of PARP activation, which can be prevented by NAC administration. Administration of 10 or 20 mg/kg 3-AB attenuated a variety of tissue injury induced by SR X-ray, including caspase-3 activation, increases in TUNEL signals and loss of testical weight. The PARP inhibitor also significantly decreased SR X-ray-induced γ-H2AX signal - a marker of DSB.
  
  
  CONCLUSIONS
  Our study has provided the first evidence suggesting that SR X-ray can induce PARP activation by generating oxidative stress, which leads to various tissue injuries at least partially by exacerbating DNA damage and apoptotic changes.
authors.affiliation: School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University , Shanghai , P. R. China.
authors.forename: Caibin
authors.initials: C
authors.lastname: Sheng
authors.forename: Heyu
authors.initials: H
authors.lastname: Chen
authors.forename: Ban
authors.initials: B
authors.lastname: Wang
authors.forename: Caixia
authors.initials: C
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.forename: Yexin
authors.initials: Y
authors.lastname: Li
authors.forename: Weihai
authors.initials: W
authors.lastname: Ying
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D053148:Caspase 3 / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D004249:DNA Damage; D004789:Enzyme Activation / Q000528:radiation effects; D008297:Male; D018384:Oxidative Stress / Q000528:radiation effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017356:Synchrotrons; D013737:Testis / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D014965:X-Rays / Q000009:adverse effects
chemical_list: D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3
keywords: DNA damage; radioprotectors; rat; reactive oxygen species