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MECHANISMS OF CELL KILLING IN PHOTODYNAMIC THERAPY USING A NOVEL in vivo DRUG/in vitro LIGHT CULTURE SYSTEM
Author(s) -
Hampton James A.,
Selman Steven H.
Publication year - 1992
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 - 10.1111/j.1751-1097.1992.tb02152.x
Subject(s) - photodynamic therapy , photosensitizer , in vivo , hematoporphyrin , in vitro , tissue culture , cell culture , cancer research , intracellular , chemistry , biophysics , pharmacology , biology , pathology , medicine , biochemistry , photochemistry , genetics , microbiology and biotechnology , organic chemistry
Abstract— Photodynamic therapy of certain neoplasms has emerged as a promising form of cancer treatment. This type of therapy involves the exogenous administration of a photosensitizer with subsequent exposure to light. The ensuing photochemical reaction results in destruction of the tumor. Whether tumor cells are destroyed directly by the photodynamic treatment or indirectly as a result of destruction of the tumor microvascular bed is unknown. To address this question, methods were adapted to test whether combinations of a photosensitizer and light resulted in direct cell killing of precision cut tissue slices placed in culture. The major advantages of this culture system are that photosensitizers are administered in vivo , tissue slices produced in minutes, placed in culture medium, and irradiated in vitro . Any resulting cellular destruction occurs in the absence of a functioning vascular system and indicates that photodynamic therapy acts through a direct cell killing mechanism. Tissue slice viability was monitored by two standard methods: assay for intracellular potassium and morphological examination at the electron microscopic level. The effects of hematoporphyrin derivative and light were examined on tissue slices produced from a prostate adenocarcinoma transplanted into male Copenhagen rats. The data indicate that direct killing of tumor slices occurs and is dependent on the irradiation protocol used.