Journal
JOURNAL OF RADIATION RESEARCH
Volume 54, Issue 2, Pages 251-259Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jrr/rrs099
Keywords
gap junction permeability; cohort effects; radiotherapy; stress response; linear energy transfer; radiation quality
Funding
- National Aeronautics and Space Administration [NNJ06HD91]
- National Cancer Institute at the National Institutes of Health [CA049062]
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In multicellular organisms, intercellular communication is essential for homeostatic functions and has a major role in tissue responses to stress. Here, we describe the effects of expression of different connexins, which form gap junction channels with different permeabilities, on the responses of human cells to ionizing radiation. Exposure of confluent HeLa cell cultures to Cs-137 gamma rays, 3.7 MeV alpha particles, 1000 MeV protons or 1000 MeV/u iron ions resulted in distinct effects when the cells expressed gap junction channels composed of either connexin26 (Cx26) or connexin32 (Cx32). Irradiated HeLa cells expressing Cx26 generally showed decreased clonogenic survival and reduced metabolic activity relative to parental cells lacking gap junction communication. In contrast, irradiated HeLa cells expressing Cx32 generally showed enhanced survival and greater metabolic activity relative to the control cells. The effects on clonogenic survival correlated more strongly with effects on metabolic activity than with DNA damage as assessed by micronucleus formation. The data also showed that the ability of a connexin to affect clonogenic survival following ionizing radiation can depend on the specific type of radiation. Together, these findings show that specific types of connexin channels are targets that may be exploited to enhance radiotherapeutic efficacy and to formulate countermeasures to the harmful effects of specific types of ionizing radiation.
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