Poly(ADP-ribose) polymerase activation mediates synchrotron radiation X-ray-induced damage of rodent testes by exacerbating DNA damage and apoptotic changes

Abstract

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.

Keywords::

• DNA damage
• radioprotectors
• rat
• reactive oxygen species

Acknowledgements

We would like to express our gratitude to Prof. Xizeng Wu (University of Alabama at Birmingham, USA) for valuable advice about dose calculations. We acknowledge Jiaxiang Shao, Yunyi Hong, Yunchan Wang, Tengyuan Liu, Yingxin Ma, Hui Nie and Tingting Zhang for their technical assistance. This study was supported by a National Key Basic Research ‘973 Program’ Grant #2010CB834306 (to WY), Chinese National Science Foundation Grant #81171098 (to WY), and Shanghai Engineering Center Grant #11DZ2211000 (to WY).

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.