Gap junctional intercellular communication is not a major mediator in the bystander effect in photodynamic treatment of MDCK II cells.
Photodynamic treatment (PDT) of confluent MDCK II cells resulted in a noticeable clustering of dead cells, consistent with a significant bystander effect. Likewise, PDT of cells in microcolonies resulted in an overabundance of microcolonies that had responded to the treatment as a single unit, that is, in which either all or no cells were dead. Confluent MDCK II cells appeared to communicate via gap junction channels, while cells in microcolonies did not. Monte Carlo simulation models were fitted to the distributions of dead cells in confluent monolayers and in microcolonies. The simulations showed that the degree of the bystander effect was higher in microcolonies than in confluent cells, suggesting that gap junction communication may be involved in the bystander effect. However, when the gap junction hypothesis was tested by treatment of microcolonies with 30 microM dieldrin, an inhibitor of gap junctional intercellular communication, there was no reduction of the bystander effect, indicating that this effect was not mediated by gap junctional intercellular communication. PDT influenced phosphorylation of tyrosine residues in several proteins in the cells. Protein phosphorylation is important in cellular signaling pathways and may be involved in the bystander effect, for example by influencing the mode of cell death.
Dahle
J
J
Department of Biophysics, Institute of Cancer Research, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway.
Mikalsen
S O
SO
Rivedal
E
E
Steen
H B
HB
D000818:Animals; D002450:Cell Communication / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line / Q000187:drug effects / Q000528:radiation effects; D003198:Computer Simulation; D004026:Dieldrin / Q000494:pharmacology; D017323:Dihematoporphyrin Ether / Q000494:pharmacology* / Q000528:radiation effects; D004285:Dogs; D004847:Epithelial Cells / Q000187:drug effects* / Q000528:radiation effects; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D007668:Kidney; D008954:Models, Biological; D009010:Monte Carlo Method; D018384:Oxidative Stress; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D010777:Photochemistry; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000528:radiation effects
D017319:Photosensitizing Agents; D017323:Dihematoporphyrin Ether; D004026:Dieldrin