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 notic eable clustering of dead cells, consistent with a significant bystander eff ect. Likewise, PDT of cells in microcolonies resulted in an overabundance o f 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 appe ared 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 s howed that the degree of the bystander effect was higher in microcolonies t han in confluent cells, suggesting that gap junction communication may be i nvolved in the bystander effect, However, when the gap junction hypothesis was tested by treatment of microcolonies with 30 mu M dieldrin, an inhibito r of gap junctional intercellular communication, there was no reduction of the bystander effect, indicating that this effect was not mediated by gap j unctional intercellular communication, PDT influenced phosphorylation of ty rosine residues in several proteins in the cells. Protein phosphorylation i s important in cellular signaling pathways and may be involved in the bysta nder effect, for example by influencing the mode of cell death, (C) 2000 by Radiation Research Society.