In order to apply photodynamic therapy to pigmented neoplasms, comparative photosensitizing studies of B 16 pigmented melanoma in C 57 B 1/6 mice were carried out with haematoporphyrin derivative (HpD), zinc(II) phthalocyanine ( ZnPc ), zinc(II) naphthalocyanine ( ZnNc ) and tetrabenzamido-substituted zinc(II) naphthalocyanine ( ZnNcA ). By injection of the optimal drug concentration and application of the optimal dose of light irradiation (the emission of the laser dye corresponding to the λmax value of the respective sensitizer) a phototherapeutic effect was observed only after photosensitization with the longest-wavelength-absorbing sensitizer, namely ZnNcA . It is supposed that the detected, through different assessment criteria, promising phototherapeutic effect after ZnNcA photosensitization of B 16 pigmented melanoma in mice is due to suitable structural, photophysical and photochemical properties of this sensitizer, but not due to a hyperthermic effect. This assumption is supported by the results obtained after irradiation of B 16 pigmented melanoma-bearing mice with the same fluence rate and fluence but without the sensitizer. In this case the tumour temperature did not increase by more than 35 °C and no changes in the mean tumour diameter or in the malignant subcellular components were detected.
Cytotoxicity induced by photodynamic therapy (PDT) is connected with the phenomena of photooxidation. Generation of singlet oxygen and free radicals (superoxide or hydroxide) is accepted as a mechanism for the photo-oxidation action of PDT. Very little is however known about the validity of metabolitic and biochemical events observed in cell culture systems to in vivo tumor shrinkage following PDT. In the present work using the wellstudied tetrabenzamido-substituted zinc (II)-naphthalocyanine (ZnNc) including towards pigmented melanoma, we accessed its efficacy for apoptotic processes during PDT of Lewis lung carcinoma (LLC) in mice in dependence on light intensity. Early photodynamic therapy responses were examined at 1, 3, 6, 10 and 24 h after coherent 774 nm illumination of the tumors applied 24 h after intraperitoneal (i.p.) injection of dipalmitoylphosphatidylcholine (DPPC)-liposome-incorporated 0.5 mg kg À1 b.w. ZnNc. Fluence rates of 260, 380 and 500 mW cm À2 at a fluence of 360 J cm À2 were used. Macroscopic observations showed that tumor reduction (and its eventual elimination) depends on optimal conditions for the occurring of photochemical reaction during PDT. At the same time, electron microscopy (EM) assays demonstrated strongly expressed dependence of apoptotic processes on the applied light intensities. Features of apoptotic processes were most clearly expressed at the highest used fluence rate.
The tyrosinase activity in two sucrose gradient isolated melanosome fractions from a melanotic hamster melanoma was found to increase after alpha-chymotrypsin treatment. The enhancement in tyrosinase activity had its maximum at a concentration of 1 mg/ml alpha-chymotrypsin after 120 min incubation at 37 degrees C. No direct activating effect of alpha-chymotrypsin was found either on the soluble tyrosinase fraction from freshly prepared untreaed whole-tumor homogenate or on purified mushroom tyrosinase. The activating effect of alpha-chymotrypsin upon the melanosome tyrosinase is believed to be due to the endopeptidic hydrolysis of the--CO--NH--bound existing between tyrosinase and tyrosine and phenylalanine residues in the melanin molecule. Although alternative interpretations are not excluded, the observed enhancement in tyrosinase activity after alpha-chymotrypsin treatment of melanosomes might indicate the existence of an "enzyme liberating" mechanism in the melanosomes.
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