摘要:

Abstract—Electrophilic compounds metronidazole (METRO) and misonidazole (MISO), considerably enhance the photooxidation quantum yield of Type I photodynamic substrates such as Trp, Tyr and Cys. For the latter, the quantum yield of photooxidation which can be much greater than one, suggests radical chain reactions. On the other hand, METRO and MISO inhibit1O2formation because they react at diffusion controlled rate (∼109M−1S−1) with porphyrin triplets forming, porphyrin radical cations. As a result, the porphyrins are still able to photosensitize the destruction of Type I substrates even in the absence of O2. These results are discussed with respect to the possibility of increasing the sensitivity of hypoxic cells to porphyrin photosensit

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1986.tb05599.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Abstract—Exposure of oligomeric proteins to UV‐A irradiation in the presence of various furocoumarins results in extensive crosslinking of the enzyme subunits. The mechanism by which these covalent bridges are formed does not involve the furocoumarin moiety as the crosslinking agent, but depends upon oxidative processes, mainly involving singlet oxygen and radical mediated processes not involving oxygen. The formation of crosslinks is notper seresponsible for the inactivation of enzymes since in glutamate dehydrogenase the two reactions proceed at the same rate, in catalase it is not accompanied by enzyme inactivation and in alcohol dehydrogenase the inactivation rate is higher than polymerizat

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1986.tb05600.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Abstract—Azathioprine is used as an immunosuppressant for renal transplant recipients, but is frequently associated with severe skin cancer as a side effect. 6‐Mercaptopurine, the primary metabolite of azathioprine. absorbs strongly in the UVA region and displays substantial photochemical reactivity. The primary photochemical processes in aqueous solution are triplet state formation and photoionization, as shown by flash photolysis. In oxygenated solution, singlet oxygen and superoxide are produced, and ground state 6MP appears to react with these species. Glutathione inhibits this reaction and is itself oxidized. In deoxygenated solution, reactions implicating the thiyl radical and hydrogen atom and electron transfer occur as shown by reaction with histidine and p‐nitrosodimethylaniline. Nitro Blue Tetrazolium or acryl

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1986.tb05601.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Abstract—The photochemical reactivity of the immunosuppressant drug, azathioprine (AZT) and two representative metabolites of the nitroimidazole moiety, 1‐methyl‐4‐nitroimidazole (MNI) and lmethyl‐4‐nitro‐5‐thioimidazole (MNTI) has been examined. No transient species of AZT were observed by laser flash photolysis, inferring a low triplet yield or its rapid deactivation. Consequently AZT, MNI and MNTI displayed little or no photodynamic sensitizationviaphotooxidation reactions. However, AZT and MNI are highly reactive radical scavengers when photoexcited, as determined by reaction with polyacrylamide radicals. The photoreactivity of the metabolites of AZT is greater than that of the parent drug. an observation which may be relevant to the photocarcino

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1986.tb05602.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Abstract—Photohemolysis has been investigated extensively during the past 20 years, but the membrane target has eluded identification. It is proposed here that the target is the dimer of the band 3 anion exchange protein. This new hypothesis is based on three observations from the literature: (1) the kinetics of photohemolysis sensitized by exogenous sensitizers or induced by UV light obey a power dependence with light dose, with an exponent near two. From target theory this implies a two‐component target. (2) Band 3 molecules exist in the erythrocyte membrane as dimers. (3) Binding of eosin to band 3viaan isothiocyano group markedly increases its potency to sensitize hemolysis. Experiments with eosin isothiocyanate bound to band 3 show that lytic rate varies as the 1.45 power of light dose, and that the bound sensitizer bleaches considerably, thereby blunting the effectiveness of higher light do

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1986.tb05603.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Abstract—Patterns of mortality in a series of photocarcinogenesis experiments were examined. All experiments involved chronic irradiation of genetically non‐haired mice with simulated sunlight from a Xe lamp. Experimental variables included genetic origin of the test animals, incident dose of radiation, and the spectral quality of the radiation. In 16 experiments involving 10 genetic origins of mice the following patterns were detected: (1) survival was inversely proportional to the delivered radiation dose; (2) within origins the life‐shortening efficacy of radiation was closely correlated with its carcinogenic efficacy; (3) between genetic origins the carcinogenicity and lethality of a radiation dose were qualitatively correlated, but relative efficacy for the two effects varied; (4) altering the source spectrum by modifying the short‐wave (UVB) cutoff produced similar changes in carcinogenicity and lethality, suggesting that UVB was a significant contributor to lethal efficacy; (5) nature and relative timing of the carcinogenic response were such that carcinogenesis was not likely to have caused the observed mortality. It is speculated that systemic effects, possibly immunologic or toxic, are produced by chronic UV irradiation, and that these apparently cumulative, dose‐dependent effects result in premature death of non‐

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1986.tb05604.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Abstract—Hairless mice were irradiated repeatedly by exposure to unfiltered black‐light (FR74T12 PUVA) fluorescent lamps and the time to development of skin tumors was determined. For several groups of animals the treatment variable was the size of the weekly dose. A similar approach had been used previously to determine dose‐response characteristics for other ultraviolet radiation emitting sources: a xenon arc solar simulator (with a series of five cut‐off filters producing five source spectra), and a fluorescent (FS40T12) “sunlamp”. The median tumor latent period (time period for just more than one half of the animals to develop at least one tumor each) was accurately predicted for all these ultraviolet radiation emitting sources by a mathematical equation incorporating the spectral source description and a spectral weighting function. The weighting function judged most appropriate for ultraviolet radiation‐induced photocarcinogenesis was the action spectrum, determined previously, for acute (single dose) skin edema in hairless mice. The mathematical equation assigns no effectiveness to wavelengths greater than 330 nm. There was no evidence for wavelength interaction in the spectral range of 26MW nm. Our data, combined with results of others, lead us to conclude that radiation with wavelength greater than 330 nm has an average relative efficacy (297 nm =1.0) less than 0.0002, and that this efficacy is not detectable with sources in which at least 2% of the UV radiation is in t

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1986.tb05605.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Abstract—Cattle rhodopsin (11‐cis‐Rh) and isorhodopsin (9‐cis‐Rh) were prepared from the same extract of cattle opsin by incubation in the dark with 114– and 9‐cis‐retinals, respectively. The preparations obtained were mixed with glycerol (67% in the final concentration) and then cooled to 77 K by a rapid cooling method for freezing the samples as a clear glass, without any cracks. The spectral changes during their photochemical reactions were measured. A computer analysis of the spectra obtained verified that bathorhodopsin from 11‐cis‐Rh was identical in spectrum with that from 9‐cis‐Rh not only in photosteady state but also under a

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1986.tb05606.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Abstract—The 11‐cis and all‐trans isomers of a series of poly(ethylene glycol)‐oligopeptide ‐ Schiff bases as models for rhodopsin were synthesized and studied. Absorption data for certain of the PEG‐peptide Schiff bases demonstrated that no intramolecular hydrogen‐bonding (or protonation) occurs between the Schiff base and an acidic amino acid residue, as was previously thought. Photoisomerization of the 11‐cis protonated and unprotonated Schiff bases were examined using both steady state and laser flash techniques. Also with 355 nm excitation (and additionally 532 nm in one case), an approximate 40% increase in quantum yield of isomerization (φ) occurred for all protonated PEG‐peptide Schiff bases compared to the H+‐n‐butylamine counterparts (in methanol). In one case, a>100% increase in φ was found in dichloromethane. These data show that PEG‐oligopeptide Schiff bases are still further improved models for rhodopsin compared to t

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1986.tb05607.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Abstract—A series of retinals with specific structural alterations have been synthesized to probe the bacteriorhodopsin binding site. The 4‐chloro‐, 4‐bromo‐ and 4‐iodoretinals all form pigments with bacterioopsin but undergo anin situdisplacement of the allylic halogen to form the 4‐hydroxyretinal pigment. Several naphthyl retinals were prepared which effectively extend the polyene chain and/or add bulk to the ring portion of the chromophore. All the naphthyl retinals form pigments with bacterioopsin but only the pigment containing the derivative with a polyene side chain identical to that of retinal pumps protons efficiently. The 12‐butyl‐13‐desmethylretinal was also synthesized but this analogue did not form a pigment with bacterioopsin. These results confirm the nonspecificity at the ring portion of the chromophore binding site and the importance of the role of the polyene chain in the proton pumping function o

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1986.tb05608.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY