Connexins and cyclooxygenase-2 crosstalk in the expression of radiation-induced bystander effects

  • Zhao Y
  • De Toledo S
  • Hu G
 et al. 
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Abstract

BACKGROUND: Signalling events mediated by connexins and cyclooxygenase-2 (COX-2) have important roles in bystander effects induced by ionising radiation. However, whether these proteins mediate bystander effects independently or cooperatively has not been investigated.

METHODS: Bystander normal human fibroblasts were cocultured with irradiated adenocarcinoma HeLa cells in which specific connexins (Cx) are expressed in the absence of endogenous Cx, before and after COX-2 knockdown, to investigate DNA damage in bystander cells and their progeny.

RESULTS: Inducible expression of gap junctions composed of connexin26 (Cx26) in irradiated HeLa cells enhanced the induction of micronuclei in bystander cells (P
CONCLUSIONS: Junctional communication and COX-2 cooperatively mediate the propagation of radiation-induced non-targeted effects. Characterising the mediating events affected by both mechanisms may lead to new approaches that mitigate secondary debilitating effects of cancer radiotherapy.

Author-supplied keywords

  • connexin channel permeability
  • connexin26/connexin32
  • cyclooxygenase-2
  • genomic instability
  • mitogen-activated protein kinase pathway
  • radiation bystander effects

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Authors

  • Y. Zhao

  • S. M. De Toledo

  • G. Hu

  • T. K. Hei

  • E. I. Azzam

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