摘要:

AbstractRhabdomyosarcoma tumors in rats made hyperglycemic by multiple injections of glucose exhibited a transient decrease in pH and an increased ability to accumulate derivatives of hemato‐porphyrin (HPD). Photoradiation of tumors in glucose/HPD‐treated animals produced a greater cell kill than in galactose/HPD‐treated controls. A therapeutic benefit of glucose administration in conjunction with HPD‐phototherapy is su

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1989.tb04102.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

AbstractIt is generally accepted that both promazine (PZ) and chlorpromazine (CPZ) photoionize monophotonically to their respective cation radicals and the corresponding hydrated electrons. It is also supposed that this photoionization has a role in the phototoxic effects of these drugs. However, using laser flash photolysis, we have observed that photoionization of CPZ during S, excitation (Λ>300 nm) is a stepwise biphotonic process. In the case of PZ our flash photolysis results are less clear‐cut, but are consistent with stepwise biphotonic photoionization for S, excitation. We demonstrate, using computer simulation of the intramolecular kinetics, that the estimated triplet state lifetime of CPZ is sufficiently long (23 ns at room temperature) to account for the apparent monophotonic photoionization that has been observed by others at high light intensities and short pulse times. Our laser flash photolysis results also suggest that the photo‐ionization mechanism of PZ and CPZ is wavelength‐dependent. Both drugs exhibit apparent monophotonic photoionization when they are excited at 266 nm under conditions of laser pulse width and intensity similar to those at 355 nm. We suggest that photoionization is not an important mechanism in the observed phototoxic and photoal‐lergic effects of PZ and CPZ in

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1989.tb04103.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

AbstractPhotolysis of gilvocarcin (GV) at 405 nm in argon saturated dimethylsulfoxide (DMSO) or 50% DMSO‐water solutions in the presence of the sodium salt of 3,5‐dibromo‐2,6‐dideutero‐4‐nitrosobenzene sulfonic acid (DBNBS‐d2) generates the CH3‐DBNBS‐d2spin adduct. It is postulated that this spin adduct is produced by photoreduction of DMSO by GV and the consequent formation and trapping of the generated methyl radicals. Gilvocarcin V also photoreduces oxygen and methyl viologen with quantum yields of 0.019 and 0.0012 respectively. The quantum yield for singlet oxygen formation by GV in DMSO, determined by measuring the rate of production of the nitroxyl radical produced by the reaction of 2,2,6,6‐tetramethylpiperidinol with singlet oxygen, was found to be 0.15. Thus, GV photochemistry proceeds by both Type I and Type II pathways which could contribute to the reported GV phototoxicity in

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1989.tb04104.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

AbstractSeveral reports in the late 1950s and early 1960s indicated that ultraviolet irradiation of dilute solutions of cytosine or 5‐methylcytosine in aliphatic alcohols, such as methanol or ethanol, leads to reaction mixtures containing products with an absorption maximum around 300 nm. The present work reports the isolation and characterization of the products responsible for this absorption in the photochemical reactions of cytosine and 5‐methylcytosine with methanol, ethanol and 2‐propanol at concentrations in the neighborhood of 200 μM. Under these conditions the reactions have been shown, in each nucleobase/alcohol system, to give almost exclusively a single type of primary photopro‐duct; each product shows an absorption maximum in the region of 300 nm. Structural analysis showed the products to be alcohol adducts with an ester linkage at C2 of the ring‐opened base and an enamine structure at C6. For example, in the case of the reaction of cytosine with methanol, the product is N‐carbomethoxy‐3‐aminoacrylamidine (IIIa). The occurrence of this type of photoreaction suggests a mode by which alcoholic functional groups on amino acid side chains could contribute to photoinduced DNA‐pro

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1989.tb04105.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

AbstractThe reactions occurring when 2‐methoxycytosine (4‐amino‐2‐methoxypyrimidine) (I) and 2‐ethoxycytosine (II) are irradiated in aqueous phosphate buffer at pH 7 have been studied. We have verified the previous results of Moore [Can. J. Chem.41, 1937–1950 (1963)], who studied I and indicated that the product isolatable in greatest yield is N‐carbomethoxy‐3‐hydroxyacrylamidine (IIIa). Similarly, we have found that the product of highest yield, isolated after irradiation of II, is N‐carboethoxy‐3‐hydroxyacrylamidine (IIIb). Evidence is presented indicating that these are secondary products, being produced through hydrolysis of the corresponding N‐carboalkoxy‐3‐aminoacrylami‐dines. Spectroscopic data are given for N‐carboisopropoxy‐3‐hydroxyacrylamidine (IIIc), as well as the N‐carbomethoxy, N‐carboethoxy and N‐carboisopropoxy derivatives of 3‐hydroxy‐2‐methylacryla‐midine. These four compounds were obtained through hydrolysis of the corresponding N‐carboalkoxy derivatives of 3‐aminoacrylamidine or 3‐amino‐2‐methylacrylamidine, isolated from the photoreaction

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1989.tb04106.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

AbstractSome new, ring‐substituted phthalocyanines have been synthesized and underwent preliminary testing for photodynamic activity using the colony forming ability of Chinese hamster cells in culture as an endpoint. Using 4‐(3‐N, N‐diethylaminopropyl)phthalonitrile as a precursor, the previously unknown metal‐free 2,9,16,23‐tetra‐(3‐N, N‐diethylaminopropyl)phthalocyanine was prepared and converted to its zinc (II) and its cationic water‐soluble 2,9,16,23‐tetramethylammonium zinc (II) iodide derivatives. Other new phthalocyanine derivatives tested, include a 2,9,16,23‐tetra(2‐hydroxymethyl‐2‐methyIbutoxy)phthalocyaninato zinc (II) and 2,3,9,10,16,17,23,24‐octahydroxyphthalocyaninato zinc (II) derivatives. Boron tribromide cleavage of the newly prepared and fully characterized 2,3,9,10,16,17,23,24‐octamethoxyphthalocyanine gave the unstable metal‐free octahydroxyphthalocy‐anine, which could only be characterized by ultravi

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1989.tb04107.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

AbstractA chalcogenapyrylium dye 8b, which is under investigation for the photodynamic therapy of malignant gliomas (brain tumors), was evaluated for inhibition of mitochondrial function both before and after exposure to laser light of 800 nm. Neoplastic and normal cells forced to use mitochondrial substrates were killed by the light‐activation of intracellular 8b as well as exposure to classic mitochondrial inhibitors, rotenone and sodium azide. Correspondingly, cells in glucose‐rich media showed little decrease in viability due to the photolysis of intracellular 8b or the presence of mitochondrial toxins. The toxicity of 8b without light activation was found to be the same regardless of the cell's energy source. Measurement of cellular ATP generated during treatment also showed the photolysis of intracellular 8b to be more inhibitory towards mitochondrial function than the unactivated parent compound. We conclude that the chalcogenapyrylium dyes localize to the mitochondrion and that photoactivation results in mitochondrial inj

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1989.tb04108.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

AbstractRose bengal photosensitized the formation of frank single‐strand breaks (SSBs) in double‐stranded, supercoiled pBR322 DNA as measured by neutral agarose electrophoresis. The yield of SSBs followed first order kinetics with respect to light fluence and dye concentration. The efficiency of cleavage was more than 20 times greater in an argon atmosphere than in an oxygen atmosphere. The quantum yield in an air atmosphere was 1.7 (± 0.3) × 10‐8. Sodium azide quenched the cleavage more efficiently in an oxygen atmosphere than when the oxygen concentration was reduced. Isopropanol and mannitol were poor quenchers; ribose‐5‐phosphate and guanosine‐5'‐monophosphate did not quench the cleavage. Substituting D2O for H2O increased the yield of SSBs in both oxygen and oxygen‐depleted atmospheres. The results are consistent with initiation of cleavage by reaction of the triplet state of rose bengal (or a radical derived from it) with DNA. In the presence of oxygen, an additional mechan

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1989.tb04109.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

AbstractThe relationship between levels ofin vivoaccumulated photosensitizer (Photofrin II), photodynamic cell inactivation uponin vitroorin vivoillumination, and changing tumor oxygenation was studied in the radiation‐induced fibrosarcoma (RIF) mouse tumor model.In vivoporphyrin uptake by tumor cells was assessed by using14C‐labeled photosensitizer, and found to be linear with injected photosensitizer dose over a range of 10 to 100 mg/kg. Cellular photosensitivity upon exposurein vitroto 630 nm light also varied linearly within vivoaccumulated photosensitizer levels in the range of 25 to 100 mg/kg injected Photofrin II, but was reduced at 10 mg/kg. Insignificant increases in direct photodynamic cell inactivation were observed followingin vivolight exposure (135 J/cm2, 630 nm) with increasing cellular porphyrin levels. These data were inconsistent with expected results based onin vitrostudies. Assessment of vascular occlusion and hypoxic cell fractions following photodynamic tumor treatment showed the development of significant tumor hypoxia, particularly at 50 and 100 mg/kg of Photofrin II, following very brief light exposures (1 min, 4.5 J/cm2). The mean hyupoxic cell fractions of 25 to 30% in these tumors corresponded closely with the surviving cell fractions found after tumor treatmentin vivo, indicating that these hypoxic cells had been protected from PDT damage. Inoculation of tumor cells, isolated from tumors after porphyrin exposure, into porphyrin‐free hosts, followed byin vivoexternal light treatment, resulted in tumor control in the absence of vascular tumor bed effects at high photosensitizer doses only. These results indicate that the prerequisites for tumor destructionviadirect photodynamic tumor cell inactivationin vivoare high photosensitizer content in tumor cells and relative insensitivity of the tissue microvasculature. Under conditions where the tumor bed is sensitive to photodynamic damage, tumor cell kill can occur at a wider range of photosensitizer levels as a consequence of PDT induced isc

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1989.tb04110.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

AbstractSkin photosensitivity of sun exposed sites is the major side effect of dihaematoporphyrin ether (DHE) photodynamic therapy (PDT). Reports of severe oedema and erythema have generally been anecdotal. We have studied aluminium sulphonated phthalocyanine (AlSPc) as a potential photosensitiser for PDT. In this paper we report our work comparing the skin photosensitivity reactions of DHE and AlSPc. We have studied: (i) the time course of the skin reactions, (ii) the effect of increasing time from administration of photosensitiser to irradiation, (iii) drug‐skin reaction dose response. Groups of Skh I female hairless albino mice were given an intravenous bolus dose of either 0.9% saline solution, AlSPc or DHE (Photofrin II). Drug doses ranged from 0.5 to 50 mg/kg. At times ranging from 1 h to 1 month animals were irradiated with a range of doses of solar simulated radiation (SSR). The skin reaction was observed over a 2 week period. DHE reactions were always more severe than those with AlSPc. Peak skin reaction was seen at 3 h for DHE and 6 h for AlSPc. DHE reactions were still visible 2 weeks after irradiation whereas the AlSPc reaction disappeared by 48 h. Irradiation evoked a reaction up to 2 months after administration of DHE but only up to 2 weeks with AlSPc. The mean SSR dose at which a skin reaction was seen decreased with increasing dose of both agents. The rate of decrease was slower with AlSPc than DHE. This study suggests that in PDT, AlSPc will cause much less skin photosensitivity than DH

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1989.tb04111.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY