Mitochondria-dependent signalling pathway are involved in the early process of radiation-induced bystander effects

• Published in: British journal of cancer Vol. 98; no. 11; pp. 1839 - 1844
• Main Authors: Chen, S, Zhao, Y, Han, W, Zhao, G, Zhu, L, Wang, J, Bao, L, Jiang, E, Xu, A, Hei, T K, Yu, Z, Wu, L
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.06.2008; Nature Publishing Group
• Subjects: Animals; Apoptosis; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Bystander Effect - radiation effects; Calcium - metabolism; Cancer Research; Cancer therapies; Cell Line; Cricetinae; Cytoplasm; DNA, Mitochondrial - physiology; Drug Resistance; Electron Transport; Epidemiology; Fibroblasts; Histones - biosynthesis; Humans; Medical research; Medical sciences; Mitochondria; Mitochondria - physiology; Mitochondrial DNA; Molecular Diagnostics; Molecular Medicine; Nitric oxide; Nitric Oxide - biosynthesis; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - physiology; Oncology; Radiation; Reactive Oxygen Species - metabolism; Signal Transduction - physiology; Superoxides - metabolism; Tumors; New York; United States > US; radiation-induced bystander effects; nitric oxide synthase; signalling pathway; mitochondrion; Enzyme; Bystander effect; Nitric-oxide synthase; Mitochondria; Cancerology; Signaling pathway; Radiation effect; Early; Oxidoreductases
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6604358

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 ( ρ 0 ) A L or normal ( ρ + ) 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 γ -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 γ -H2AX induction and that radiation could stimulate cellular NO and O 2 •− production in irradiated ρ + A L cells, but not in ρ 0 A L cells. These observations, together with the findings that ruthenium red treatment significantly reduced the NO and O 2 •− levels in irradiated ρ + 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.