摘要:

AbstractVery little is known about the applicability of the metabolic and biochemical events observed in cell culture systems toin vivotumor shrinkage following photodynamic therapy (PDT). The purpose of this study was to assess whether PDT induces apoptosis during tumor ablationin 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 byin vivoPDT may activate endonucleolysis and chromatin condensation, and that apoptosis is an early event in tumor shrinkage

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1993.tb04969.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

AbstractTriplet state and photoinduced charge separation dynamics under adsorption was Confirmed for the first time for the polymer without or with coadsorbed electron acceptor, respectively. The absorption spectrum of the triplet polymer is similar to the Tn← T1band ofN‐ethylcarbazole, showing no appreciable interchromophoric interaction. Absorption spectra of the coadsorbed systems comprise the polymer cation and electron acceptor anion. The ion radicals on the cellulose substrate undergo mutual recombination, and simple uni‐ and bimolecular decay kinetics do not hold. This mechanism was compared with that for poly(N‐vinylcarbazol

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1993.tb04970.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

AbstractThe absorption and emission characteristics of five hydroxytetrahydrochrysenes substituted with acceptor groups (nitro, cyano, methylketone, 1° amide and methyl ester) (THC‐NO2, THC‐CN, THC‐COCH3, THC‐CONH2and THC‐CO2CH3, respectively) were investigated in an extensive set of solvents. The order of absorption and fluorescence bathochromicity are: THC‐NO2>THC‐COCH3>THC‐CN ≥ THC‐CO2CH3>THC‐CONH2and THC‐NO2>>THC‐COCH3>THC‐CO2CH3>THC‐CN>THC‐CONH2, respectively. The emission spectra of these compounds are sensitive to the solvent polarity (ET[30] scale) in the order: THC‐NO2>THC‐COCH3>THC‐CO2CH3>THC‐CONH2>THC‐CN. The response of the emission maxima of these compounds to the solvent polarity and hydrogen‐bond donor/acceptor properties (π*/α/β and acity/basity scales) was also determined. The emission energies of THC‐NO2were most sensitive to π*, β, acity, and basity of the solvent; those of the amide were least sensitive to the solvent π*, β, and basity.The ground‐ and excited‐state dipole moments were determined by semiempirical molecular orbital calculations and the absorption/fluorescence solvent‐shift method, respectively. THC‐NO2had the largest ground‐ and excitedstate moments. The ester and amide had the smallest ground‐ and excited‐state moments, respectively. In general, unsatisfactory results were obtained for correlations of the emission and absorption energies, fluorescence solvatochromism and the ground‐ and excited‐state dipole moments with the Hammett substituent constants of the five acceptor groups. Acceptable correlations were obtained for the absorption and emission energies and the fluorescence solvatochr

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1993.tb04971.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

AbstractIncreasing evidence of the role of magnesium in various cellular mechanisms has led to the need to develop an accurate method for the evaluation of magnesium concentration in cells. 1H‐indole‐6‐carboxylic acid, 2–(4‐bis‐[carboxymethyl]amino‐3–[carboxy]ethoxy) (mag‐indo‐1) is used as a fluorescent indicator for ionized magnesium concentration. A physicochemical study of this probe has pointed out (1) that at concentrations higher than 10 μM, the presence of dimers can alter the different equilibria and (2) at concentrations, avoiding the dimer (≤ 10 μM), three fluorescent forms are in equilibrium with the deprotonated form of mag‐indo‐1 (L), which are the protonated form LH, the magnesium‐bound form LM and the protein‐bound form LP. A model is proposed that takes into account the equilibria between the four species. In a solution containing magnesium and protein, a complex fluorescence spectrum can be resolved by a combination of the three fluorescence spectra (L, LM, LP). However, under these conditions, the LH fluorescence spectrum is not taken into account for the spectral resolution. Finally, from the contribution of characteristic fluorescence spectra in the experimental fluorescence spectrum, the magnesium concentration can be estimated with accuracy. Such a method should be further applied to magnesium determ

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1993.tb04972.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

AbstractWe propose the use of acetoxymethyl esters of pH‐sensitive amphipathic photosensitizers (PS) for photodynamic therapy (PDT). These compounds may be applicable for PDT involving endocytosis of lipophilic carriers leading to lysosomal uptakc of the esterified PS by target cells. Partial and/or total enzymatic de‐esterification may result in the extralysosomal distribution of the photoactive agents, possibly culminating in a multisite photochemical response. We report here the synthesis and properties of chlorine6triacetoxymethyl ester (CAME) and pheophorbideaacetoxymethyl ester (PAME). Chlorine6and pheophorbideaare photocytotoxic chlorins that possess free carboxylate groups and exhibit optimum wavelengths of excitation substantially red shifted relative to hematoporphyrin derivative. Acetoxymethyl esterification of chlorine6and pheophorbideawas accomplished with bromomethyl acetate. High‐performance liquid chromatography allowed for the purification of PAME, in 87% purity, and CAME, in 63% yield and 94% purity, as well as the detection of the presumed mono‐ and diesters of chlorine6as transient intermediates in the synthesis of CAME. The ultraviolet‐visible absorption, fluorescence excitation and emission, NMR and mass spectra of the chlorine6tnester are consistent with those expected for CAME. The pH‐sensitive amphipathicity of pheophorbideaand chlorine6but not CAME was demonstrated using a water/1‐octanol partition assay. The production of pheophorbideafrom PAME and the sequential formation of the di‐ and monoesters and free chlorine6from CAME, by the action of lysosomal esterases obtained from cancer cells, demonstrate the potential of cellular enzymes to convert the lipophilic esters to pH‐sensitive amphipathic PS. It is expected that the product of the esterases' action in the acidic lysosome will be hydrophobic and tend to diffuse into the organelle membrane. Contact with the neutral pH of the adjacent cytosol will result in conversion of the PS to a more hydrophilic anionic species, presumably allowing for it lo diffuse into that compartment and partition throughout the lipophilic and aqueous compart

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1993.tb04973.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

AbstractThe proteins induced by heat and other stressors, called heat shock proteins (HSP) or stress proteins, are considered to play a general role in protection from cellular injury. Exposure to UVA (320400 nm) following application of 8‐methoxypsoralen (8‐MOP), termed PUVA is commonly used in the field of dermatology. In order to understand the induction of HSP in PUVA‐treated human skin, indirect immunofluorescence using a monoclonal antibody specific for the 72 kDa HSP (HSP 72) was carried out in organ‐cultured normal human skin that was treated with PUVA. When the organ‐cultured skin was treated at 37°C for 1 h with 8‐MOP at a final concentration of 10 or 100 μg/mL and exposed to UVA (51.3 kJ/m2), nuclear immunofluorcscence of HSP 72 was detected in the epidermal cells 12 h after UVA irradiation. In contrast, the induction of HSP 72 was not detected either by UVA irradiation or 8‐MOP treatment. These results suggest that PUVA treatment is one of the stressors for human skin, and DNA damage caused by PUVA

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1993.tb04974.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

AbstractLyophilized aged garlic extract has been incorporated at concentrations of 0.1%, 1% and 4% by weight into semipurified powdered diets and fed to hairless mice. Under moderate UVB exposure conditions resulting in 58% suppression of the systemic contact hypersensitivity response in control‐fed mice, a dose‐responsive protection was observed in the garlic‐fed mice; contact hypersensitivity in the UVB‐exposed mice fed 4% garlic extract was suppressed by only 19%. If the UVB exposure was replaced by topical application of one of a series of lotions containing increasing concentrations ofcis‐urocanic acid, a dose‐responsive suppression of contact hypersensitivity was demonstrated in control‐fed mice (urocanic acid at 25, 50, 100 and 200 μg per mouse resulting in 22–46% suppression). Mice fed a diet containing 1% aged garlic extract were partially protected fromcis‐urocanic acid‐induced suppression of contact hypersensitivity, with greater protection from the lower concentrations of urocanic acid. Mice fed a diet containing 4% aged garlic extract were protected from all concentrations of urocanic acid. The results indicate that aged garlic extract contains ingredient(s) that protect from UVB‐induced suppression of contact hypersensitivity and suggest that the mechanism of protection is by antagonism of thecis‐urocanic acid mediation of this f

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1993.tb04975.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

AbstractGilvocarcin V (GV), a coumarin, is a nucleic acid photosensitizer that is phototoxic to bacteria and mammalian cells at picomolar levels in the presence of near‐UV radiation (UVA). We evaluated the effectiveness of GV plus UVA for inactivation of several viruses, including herpes simplex virus, type 1 (HSV) and the bacterial viruses φX174, T7, PRD1 and φ6. Some inactivation of the bacterial viruses was observed with UVA radiation alone (4–50% survival at 26 kJ/m2). Additional photosensitized inactivation was observed only with T7 and φ6 at 2.0 μMGV. On the other hand, HSV was photoinactivated with concentrations of GV three orders of magnitude lower (1.0 nM). Similar to the case with UV (254 nm) inactivation, the GV‐UVA survival curve for HSV indicated multicomponent inactivation kinetics, which could not be explained by photobleaching of GV. The wide range of photosensitivities of these viruses to GV cannot be adequately explained by models based only on viral nucleic acid content or presence of lipid

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1993.tb04976.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

AbstractThe effects of cell differentiation and mitogen and phorbol ester stimulation on the formation of 8‐methoxypsoralen (8‐MOP)‐DNA photoadducts in murine T lymphocytes were examined using3H‐8‐MOP. While there were no significant differences in 8‐MOP photoadduct formation among BALB/c thymocytes, splenocytes, splenic T cells and MRL/1pr lymph node cells, BALB/c bone marrow cells showed fewer photoadducts than did the lymphocytes. This suggested that proliferating progenitor cells may be resistant to 8‐MOP photoadduct formation. Incubation of purified splenic T cells with lectin mitogens for 2 h or with phorbol 12‐myristate 13‐acetate (PMA) for 2–43 h resulted in reduction of 8‐MOP photoadduct formation in the DNA, whereas 64 h cultivation with these agents augmented the photoadduct formation. The reduction of photoadduct formation induced by phytohemagglutinin was restored by the further addition of a protein kinase C (PKC) inhibitor, H‐7, to the culture. Thus, it is assumed that the reduction of adduct formation evoked by mitogens and PMA is mediated in part by the activation of PKC in the cells. On the other hand, the augmentation of the adduct formation induced by the longer‐period cultures with mitogens and PMA appeared to be caused by down‐regulation of PKC. The present study showed that the stimulatory signals in which PKC is presumably involved affect the ability of cells to

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1993.tb04977.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

AbstractEffects on lens physiology of UVB and UVA used separately and sequentially were investigated using 4 week old rabbit lenses in organ culture. Narrowband UVB at 0.3 J/cm2= joules/lens (1 h exposure) has little effect on sodium and calcium concentrations in the lens interior or transparency of lenses subsequently cultured for 20 h after a 1 h exposure. With an incident energy of 3 J/cm2of broadband UVB (295–330 nm), lenses become opaque and slightly swollen with significant ion imbalances during culture over a 1 day period. In contrast, lenses exposed to approximately 6–24 J/cm2of UVA (330–400 nm) remain transparent after 1 day of culture. Extended culture up to 4 days reveals no signs of opacification. Ion homeostasis and normal lens hydration are also maintained in UVA‐irradiated lenses. The presence of 95% oxygen during UVA irradiation is also without effect. Broadband UVA irradiation is damaging, however, if lenses are first exposed to subthreshold doses of narrowband UVB (307 ± 5 nm) irradiation,viz. 0.3 J/cm2. Thus, sequential UVB/UVA irradiation at subthreshold doses causes impaired active cation transport and accumulation of sodium and calcium accompanying lens opaci

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1993.tb04978.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY