Direct evidence for the participation of gap junction-mediated intercellular communication in the transmission of damage signals from alpha -particle irradiated to nonirradiated cells

We have examined this hypothesis by exposing cells to very low fluences of ␣-particles, similar to those emitted by radon gas, such that as few as 1% of the cells in a population are traversed by a particle and receive any radiation exposure

E. I. Azzam

2002

Scholarcy highlights

  • It has generally been considered that important biological effects of ionizing radiation arise as a direct consequence of DNA damage occurring in irradiated cells
  • By using the endpoints of p53 and p21Waf1 expression and induction of DNA damage, we present direct evidence for the involvement of connexin43-mediated intercellular communication, by in situ immunofluorescence techniques and by the use of cells genetically compromised in their ability to perform gap junction-mediated intercellular communication
  • I t has long been thought that the important biological effects of radiation in a cell population are a direct consequence of DNA damage occurring in the irradiated cells: unrepaired or misrepaired DNA damage in these cells is responsible for the genetic effects of radiation
  • The gene expression data obtained in this study with confluent cultures of human and rodent cells exposed to very low fluences of ␣-particles indicate that the effects of these particles are not confined to cells whose DNA is directly damaged by a traversing particle, and they provide direct evidence for the involvement of GJIC in mediating the bystander response
  • The observation that the induction of p21waf1 expression detected in situ occurs in aggregates of neighboring gap junction-competent cells far exceeding the expected number that would receive direct DNA damage indicates clearly that nontraversed bystander cells participate in the overall response of the exposed cultures, and suggests that this response could be mediated by GJIC
  • In situ immunofluorescence analysis of p21Waf1 expression in cells lacking GJIC revealed that it was induced only in single cells that were well secluded from each other, as opposed to its induction in aggregates of cells. These data suggest that cultures of cells exposed to low fluences of ␣-particles respond as a whole to the radiation stress with similar signaling pathways induced in nontraversed and traversed cells, and directly implicate GJIC as a mechanism mediating these effects
  • These data suggest that cultures of cells exposed to low fluences of ␣-particles respond as a whole to the radiation stress with similar signaling pathways induced in nontraversed and traversed cells, and directly implicate gap junction-mediated intercellular communication as a mechanism mediating these effects

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