1. ¹Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031, People's Republic of China
2. ²Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA

Correspondence: Dr L Wu, E-mail: ljw@ipp.ac.cn

Revised 21 January 2008; Accepted 12 March 2008; Published online 13 May 2008.

Abstract

Bystander effects induced by cytoplasmic irradiation have been reported recently. However, the mechanism(s) underlying, such as the functional role of mitochondria, is not clear. In the present study, we used either mtDNA-depleted (⁰) A_L or normal (⁺) A_L cells as irradiated donor cells and normal human skin fibroblasts as receptor cells in a series of medium transfer experiments to investigate the mitochondria-related signal process. Our results indicated that mtDNA-depleted cells or normal A_L cells treated with mitochondrial respiratory chain function inhibitors had an attenuated -H2AX induction, which indicates that mitochondria play a functional role in bystander effects. Moreover, it was found that treatment of normal A_L donor cells with specific inhibitors of NOS, or inhibitor of mitochondrial calcium uptake (ruthenium red) significantly decreased -H2AX induction and that radiation could stimulate cellular NO and O₂^- production in irradiated ⁺ A_L cells, but not in ⁰ A_L cells. These observations, together with the findings that ruthenium red treatment significantly reduced the NO and O₂^- levels in irradiated ⁺ A_L cells, suggest that radiation-induced NO derived from mitochondria might be an intracellular bystander factor and calcium-dependent mitochondrial NOS might play an essential role in the process.