PURPOSES: 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 AND MATERIALS: 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.
PURPOSES: 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 AND MATERIALS: 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 transferasedUTP 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.
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Keywords:
DNA damage; radioprotectors; rat; reactive oxygen species