PMID- 23139176 OWN - NLM STAT- MEDLINE DCOM- 20131205 LR - 20231213 IS - 1349-9157 (Electronic) IS - 0449-3060 (Print) IS - 0449-3060 (Linking) VI - 54 IP - 2 DP - 2013 Mar 1 TI - Human cell responses to ionizing radiation are differentially affected by the expressed connexins. PG - 251-9 LID - 10.1093/jrr/rrs099 [doi] AB - 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 (137)Cs 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. FAU - Autsavapromporn, Narongchai AU - Autsavapromporn N AD - Department of Radiology, New Jersey Medical School Cancer Center, Newark NJ 07103 USA. FAU - De Toledo, Sonia M AU - De Toledo SM FAU - Jay-Gerin, Jean-Paul AU - Jay-Gerin JP FAU - Harris, Andrew L AU - Harris AL FAU - Azzam, Edouard I AU - Azzam EI LA - eng GR - CA049062/CA/NCI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20121108 PL - England TA - J Radiat Res JT - Journal of radiation research JID - 0376611 RN - 0 (Connexins) RN - 0 (GJB2 protein, human) RN - 127120-53-0 (Connexin 26) SB - IM MH - Bystander Effect/*physiology/*radiation effects MH - Cell Survival/*physiology/radiation effects MH - Connexin 26 MH - Connexins/*metabolism MH - DNA Damage/*physiology MH - Dose-Response Relationship, Radiation MH - Gene Expression Regulation/physiology/radiation effects MH - HeLa Cells MH - Humans MH - Radiation Dosage MH - Signal Transduction/physiology/radiation effects MH - Gap Junction beta-1 Protein PMC - PMC3589937 EDAT- 2012/11/10 06:00 MHDA- 2013/12/16 06:00 PMCR- 2012/11/08 CRDT- 2012/11/10 06:00 PHST- 2012/11/10 06:00 [entrez] PHST- 2012/11/10 06:00 [pubmed] PHST- 2013/12/16 06:00 [medline] PHST- 2012/11/08 00:00 [pmc-release] AID - rrs099 [pii] AID - 10.1093/jrr/rrs099 [doi] PST - ppublish SO - J Radiat Res. 2013 Mar 1;54(2):251-9. doi: 10.1093/jrr/rrs099. Epub 2012 Nov 8.