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Cell-to-cell interactions
in photodynamic inactivation of cells
Dahle, Jostein1,
Steen, Harald1 and Moan, Johan1
The Norwegian Radium Hospital1
Abstract-
Cells from three different cell lines (MDCK II, WiDr, V79) were treated
with four different photosensitizers and light. The resulting distributions
of dead cells in small colonies or in confluent layers were determined
by staining the cells with fluorescing dyes and counting. The dead cells
seemed to be clustered together in the same areas of confluent layers
or in the same colonies. The distributions were compared to theoretical
distributions of dead cells using models of cells dying independently
or cells dying under the influence of cell-to-cell interactions from
their neighbours (so-called bystander effect). The results indicate
that cell-to-cell interactions are involved in the inactivation of cells
after photodynamic treatment (PDT). Several artefacts that conceivably
could explain the experimental distributions have been ruled out: 1)
Cells in the same area of a confluent layer stem from the same cell
and thus conceivably could have inherited similar sensitivity to PDT
resulting in small areas of confluent layers with the same sensitivity;
2) The presence of clones with different sensitivity to PDT; 3) The
combination of synchrony and different sensitivity to PDT in different
phases of the cell cycle; 4) Inherited differences in photosensitizer
uptake. Gap junctional intercellular communication (GJIC) plays only
a minor role, if any, for the bystander effect. The degree of bystander
effect was lower for cells dying by apoptosis than for cells dying by
necrosis. Apoptotic cells have an intact plasma membrane and they round
up and detach from the other cells. In contrast, necrotic cells have
a leaky plasma membrane. Thus, soluble factors released to the medium
could conceivably play a role in mediating the bystander effect. The
water soluble antioxidant gluthatione significantly reduced the bystander
part of cell inactivation while the lipophilic antioxidant  -tocopherol
had no effect. Thus, the soluble factor mediating the bystander effect
might be an oxidant.
Keywords: photodynamic
treatment, bystander effect, cell death, cell-to-cell interactions
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