title: Human cell responses to ionizing radiation are differentially affected by the expressed connexins.
abstract: 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 γ rays, 3.7 MeV α 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.
authors.affiliation: Department of Radiology, New Jersey Medical School Cancer Center, Newark NJ 07103 USA.
authors.forename: Narongchai
authors.initials: N
authors.lastname: Autsavapromporn
authors.forename: Sonia M
authors.initials: SM
authors.lastname: De Toledo
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Jay-Gerin
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Harris
authors.forename: Edouard I
authors.initials: EI
authors.lastname: Azzam
mesh_terms: D024201:Bystander Effect / Q000502:physiology* / Q000528:radiation effects*; D002470:Cell Survival / Q000502:physiology* / Q000528:radiation effects; D000072259:Connexin 26; D017630:Connexins / Q000378:metabolism*; D004249:DNA Damage / Q000502:physiology*; D004307:Dose-Response Relationship, Radiation; D005786:Gene Expression Regulation / Q000502:physiology / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D011829:Radiation Dosage; D015398:Signal Transduction / Q000502:physiology / Q000528:radiation effects; D000097002:Gap Junction beta-1 Protein
chemical_list: D000072259:Connexin 26; D017630:Connexins; D000097002:Gap Junction beta-1 Protein; C000607042:GJB2 protein, human