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Modes of cytotoxicity associated with photodynamic therapy

We compared sites of photodamage with modes of PDT-induced cell death, using murine leukemia tumor cells in vitro. Photodamage to mitochondrial or mitochondrial/lysosomal sites, but not tot he outer membrane, evoked a rapid apoptotic response: DNA changes were observed within 10 min, chromatin fragmentation within 1 hr after PDT. When limited photodamage to the cell membrane also occurred, we observed a delayed apoptotic response; fragmented nuclei were not detected until 24 hr after PDT. More drastic membrane damage, resulting in impaired amino acid transport, prevented an apoptotic response to PDT. A hypothesis accounting for these observations is proposed. Results of in vivo studies suggest that the more efficacious sensitizes generally produce an apoptotic response to PDT, but this question is not yet fully resolved.