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

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 o...

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Bibliographic Details
Published inBritish 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
LanguageEnglish
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
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Summary: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.
ISSN:0007-0920
1532-1827
DOI:10.1038/sj.bjc.6601686