Gap junction communication dynamics and bystander effects from ultrasoft X-rays

• Published in: British journal of cancer Vol. 90; no. 7; pp. 1450 - 1456
• Main Authors: EDWARDS, G. O, BOTCHWAY, S. W, HIRST, G, WHARTON, C. W, CHIPMAN, J. K, MELDRUM, R. A
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 05-04-2004
• Subjects: Animals; Biological and medical sciences; Bystander Effect; Cancer research; Cancer therapies; Cell Communication - radiation effects; Cell death; Cell Membrane Permeability; Cells, Cultured; Chemotherapy; Communication; Connexin 43 - metabolism; Dose-Response Relationship, Radiation; Experimental Therapeutics; Gap Junctions - physiology; Kinases; Medical research; Medical sciences; Phosphorylation; Radiation therapy; Rats; Tumors; X-Rays; bystander effect; Cancerology; Dynamics; Cell junction; Fluorescence; fluorescence redistribution; X ray; ultrasoft X-rays; Gap junction; Communication
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6601686

Gap junctions provide a route for small molecules to pass directly between cells. Toxic species may spread through junctions into 'bystander' cells, which may be exploited in chemotherapy and radiotherapy. However, this may be prevented by junction closure, and therefore an understanding of the dose-dependency of inhibition of communication and bystander effects is important. Low-energy ionising radiation (ultrasoft X-rays) provides a tool for the study of bystander effects because the area of exposure may be carefully controlled, and thus target cells may be clearly defined. Loss of gap junction-mediated intercellular communication between irradiated cells was dose-dependent, indicating that closure of junctions is proportional to dose. Closure was associated with hyperphosphorylation of connexin43. Inhibition of communication occurred in bystander cells but was not proportional to dose. Inhibition of communication at higher radiation doses may restrict the spread of inhibitory factors, thus protecting bystander cells. The reduction in communication that takes place in bystander cells was dependent on cells being in physical contact, and not on the release of signalling factors into the medium.