Early morphological changes induced by photodynamic therapy in amelanotic greene melanoma implanted in the anterior eye chamber of rabbits
Morphological changes induced by photodynamic therapy (PDT) in amelanotic Greene melanoma implanted in the anterior eye chamber of rabbits were followed up to 24 h after PDT to study the development of tissue and cell damage leading to necrosis.
Immediately after PDT, blood circulation had stopped as shown by fluorescence angiography and light and electron microscopy. It was not restored during the observation period.
The first signs of tumour tissue damage, shrinkage of tumour cells and enlargement of intracellular spaces, became apparent immediately after PDT. Tissue and cell destruction increased further, and 24 h after PDT the tumours were almost completely necrotic.
The most intriguing finding, by electron microscopy, was the presence of mitochondria with fused membranes in the untreated melanoma cells and the dramatic increase of this aberration directly after PDT. Melanocytes and fibroblasts in the same regions did not exhibit these aberrant mitochondria and furthermore kept a normal fine structure after PDT. Artificially induced ischaemia led to swollen mitochondria with ballooned cristae but showed no increase in membrane fusions. PDT thus directly interferes with mitochondrial structure. Direct damage to tumour cells therefore presumably contributes to tumour necrosis.
Key wordsHaematoporphyrin derivative Photodynamic therapy Melanoma Mitochondria Light microscopy Electron microscopy Tissue and cell morphology Development of necrosis
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