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Bystander Effects in Cell Death Induced by Photodynamic Treatment, UVA Radiation and Inhibitors of ATP Synthesis ¶
Author(s) -
Dahle Jostein,
AngellPetersen Even,
Steen Harald B.,
Moan Johan
Publication year - 2001
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1562/0031-8655(2001)0730378beicdi2.0.co2
Subject(s) - bystander effect , protoporphyrin ix , hematoporphyrin , photosensitizer , photodynamic therapy , chemistry , fluorescence , porphyrin , apoptosis , irradiation , biophysics , programmed cell death , cell , biology , photochemistry , biochemistry , physics , optics , immunology , organic chemistry , nuclear physics
Confluent layers of MDCK II cells were treated with four different photosensitizers (a purified version of hematoporphyrin derivative [Photofrin], tetra(3‐hydroxyphenyl)porphine [3‐THPP], meso ‐tetra(4‐sulphonatophenyl)porphine [TPPS 4 ] and ALA‐induced Protoporphyrin IX) and irradiated with blue light, with UVA without exogenous photosensitizers, or incubated with the metabolic inhibitors carbonyl cyanide m ‐chlorophenylhydrazone and 2‐deoxy‐ d ‐glucose. Necrotic and apoptotic cells were detected about 4 h later by fluorescence microscopy. Dead cells appeared in distinct clusters in the confluent layers. The number of dead cells in these clusters was determined by manual counting and image analysis. Forty‐one of the 43 experimental distributions of dead cells in clusters were found to be significantly different from a Monte Carlo simulation of the distribution of independently inactivated cells. However, a Monte Carlo simulation model, assuming that each dead cell increased the probability of inactivation of adjacent cells, fitted 34 of the 43 observed distributions of dead cells in clusters, indicating a significant bystander effect for all the investigated treatments. The bystander‐effect model parameter, defined as a cell's increase in probability of dying when it has dead neighbors, was significantly lower for 3‐THPP‐PDT and TPPS 4 ‐PDT than for Photofrin‐PDT, ALA‐PDT and treatment with metabolic inhibitors.