Radiation-induced bystander effects in malignant trophoblast cells are independent from gap junctional communication.
It is controversially discussed that irradiation induces bystander effects via gap junction channels and/or diffusible cellular factors such as nitric oxide or cytokines excreted from the cells into the environment. But up to now the molecular mechanism leading to a bystander response is not well understood. To discriminate between both mechanisms of bystander response, (i) mediated by gap junctional communication and/or (ii) mediated by diffusible molecules, we used non-communicating Jeg3 malignant trophoblast cells transfected with inducible gap junction proteins, connexin43 and connexin26, respectively, based on the Tet-On system. We co-cultivated X-ray irradiated and non-irradiated bystander Jeg3 cells for 4 h, separated both cell populations by flow cytometry and evaluated the expression of activated p53 by Western blot analysis. The experimental design was proven with communicating versus non-communicating Jeg3 cells. Interestingly, our results revealed a bystander effect which was independent from gap junctional communication properties and the connexin isoform expressed. Therefore, it seems more likely that the bystander effect is not mediated via gap junction channels but rather by paracrine mechanisms via excreted molecules in Jeg3 cells.
Banaz-Yaşar
Ferya
F
Institute of Anatomy, University Hospital Essen, Hufelandstr. 55, 45122 Essen, Germany.
Lennartz
Klaus
K
Winterhager
Elke
E
Gellhaus
Alexandra
A
D024201:Bystander Effect / Q000528:radiation effects*; D045744:Cell Line, Tumor; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D017629:Gap Junctions / Q000528:radiation effects*; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006801:Humans; D009369:Neoplasms / Q000473:pathology*; D014327:Trophoblasts / Q000528:radiation effects*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D017630:Connexins; C000607042:GJB2 protein, human; D016159:Tumor Suppressor Protein p53; D000072259:Connexin 26