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Apoptosis during photodynamic therapy-induced ablation of RIF-1 tumors in C3H mice: electron microscopic,
S I Zaidi1, N L Oleinick, M T Zaim
1Department of Dermatology, University Hospitals of Cleveland, Case Western Reserve University, OH 44106.
Abstract:
Very little is known about the applicability of the metabolic and biochemical events observed in cell culture systems to in vivo tumor shrinkage following photodynamic therapy (PDT). The purpose of this study was to assess whether PDT induces apoptosis during tumor ablation in vivo. We treated radiation-induced fibrosarcoma (RIF-1) tumors grown in C3H/HeN mice with PDT employing three photosensitizers, Photofrin-II, chloroaluminum phthalocyanine tetrasulfonate, or Pc IV (a promising phthalocyanine developed in this laboratory). Each photosensitizer was injected intraperitoneally and 24 h later the tumors were irradiated with an appropriate wavelength of red light using an argon-pumped dye laser. During the course of tumor shrinkage, the tumors were removed at 1, 2, 4 and 10 h post-PDT for DNA fragmentation, histopathologic, and electron microscopic studies. Markers of apoptosis, viz. the ladder of nucleosome-size DNA fragments, increased apoptotic bodies, and condensation of chromatin material around the periphery of the nucleus, were evident in tumor tissue even 1 h post-PDT; the extent of these changes increased during the later stages of tumor ablation. No changes were observed in tumors given photosensitizer alone or irradiation alone. Our data suggest that the damage produced by in vivo PDT may activate endonucleolysis and chromatin condensation, and that apoptosis is an early event in tumor shrinkage following PDT.
Insights
Photodynamic therapy (PDT) triggers apoptosis, a programmed cell death, in tumors. This study confirms apoptosis occurs early during in vivo tumor ablation following PDT, validating cell culture findings.
Area of Science:
- Oncology
- Biochemistry
Background:
- Photodynamic therapy (PDT) shows promise for tumor ablation, but its biochemical mechanisms in vivo are not fully understood.
- Translating cell culture findings to in vivo tumor responses remains a challenge.
Purpose of the Study:
- To investigate if photodynamic therapy (PDT) induces apoptosis during in vivo tumor ablation.
- To correlate in vitro observed metabolic and biochemical events with in vivo tumor shrinkage after PDT.
Main Methods:
- Radiation-induced fibrosarcoma (RIF-1) tumors in mice were treated with PDT using three photosensitizers.
- Tumor tissues were analyzed at various time points post-PDT for DNA fragmentation, histopathology, and electron microscopy.
Main Results:
- Apoptosis markers, including DNA fragmentation and chromatin condensation, were observed as early as 1 hour post-PDT.
- The extent of apoptotic changes increased over time during tumor ablation.
- No apoptosis was observed in control groups receiving only photosensitizer or irradiation.
Conclusions:
- In vivo photodynamic therapy (PDT) induces apoptosis, characterized by endonucleolysis and chromatin condensation.
- Apoptosis is an early and significant event contributing to tumor shrinkage following PDT.
- This study validates the applicability of cell culture findings to in vivo PDT outcomes.