摘要:

Abstract—Several lines of evidence support the hypothesis that ultraviolet radiation (UVR) is involved in the etiology of cutaneous melanoma in humans. However, progress in understanding the mechanisms involved in induction of melanotic tumors by UVR has been hindered by lack of a suitable animal model. During the course of multiple exposures (3 times/wk for 70 wk) of the South American opossum,Monodelphis domestica, to UVR, we first observed the appearance of areas of dermal melanocytic hyperplasia (MH) on the exposed skin. Post‐UVR exposure to photoreactivating light (320–500 nm) suppressed the occurrence of MH. We also observed at 100 weeks from first exposure that 10 of 46 surviving animals had developed melanotic tumors which arose, presumably, from areas of MH. Tumors on three of the 10 animals have been classified as malignant melanomas based on metastasis to lymph nodes. We conclude from these results that UVR can act as a complete carcinogen for melanoma induction and, based on the photoreactivation of MH induction, that DNA damage is involved in melanoma form

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1989.tb04123.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract—The results of molecular mechanical calculations on intercalation complexes of 3‐car‐bethoxypsoralen, 5‐methoxypsoralen, 8‐methoxypsoralen, 7‐methylpyrido[3,4‐c]psoralen (MepyPs) and 7‐methylpyrido[4,3‐c]psoralen (2N‐MePyPs) with the double stranded duodecanucleotide d(CGCGATATCGCG)2are presented. In the energy‐minimized structures, the psoralens are intercalated with their plane orthogonal to the helix axis. Stacking interactions between the furan ring of the psoralen and the adjacent bases are maximized in most derivatives studied, whereas the effect of the various substituents of the psoralen ring is to specifically push part of the molecule towards either the minor or the major groove, preventing a symmetrical intercalation (with respect to the two strands of the DNA). The relative position of the psoralen ring and of the adjacent thymine foreshadows the formation of furan‐side monoadducts in 3‐CPs, MePyPs and 2N‐MePyPs, whereas the formation of a pyrone‐side monoadduct appears as geometrically more favourable in 5‐MOP and both furan‐ and pyrone‐side monoadducts can be geometrically envisaged in 8‐MOP. A good correlation therefore exists between the more or less favourable equilibrium geometries and the experimentally observed photoreactions. The present study is the first attempt to characterize the geometrical parameters as part of a complex set of geometrical, dynamical and excited state parameters governing t

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1989.tb04124.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract—Polypeptides containing a basic amino acid close to their single tryptophan residue were irradiated with monochromatic 302 nm radiation. Tryptophan photolysis was monitored by absorption and fluorescence spectroscopy. Amino acid loss was evaluated by amino acid analysis. Only the protonated residues adjacent to tryptophan in the sequence were destroyed upon tryptophan excitation. This reaction is probably due essentially to direct interaction between the excited tryptophan and the neighbouring residue without electron solvatio

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1989.tb04125.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract—Aluminium trisulfonatophthalocyanine (AIPCS), a dye being widely advocated for use in photodynamic therapy, produces singlet oxygen with a quantum yield of 0.34 in oxygenated water at pH 7. Triplet A1PCS abstracts an electron from a variety of amines and phenols, the rate of electron transfer depending upon the thermodynamic driving force, forming the AIPCS radical anion. This latter species reduces molecular oxygen to superoxide ions with high efficiency. The triplet state also abstracts an electron from biological components, including NADH, vitamin C, cysteine, methionine, tyrosine, tryptophan, uracil, and guanine, but not from DNA. These results suggest that photoinduced electron abstraction from appropriate biomaterials could compete with singlet oxygen production underin vivocondition

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1989.tb04126.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract—We report on a study of the photoexcited triplet state, at low temperatures in ordered liquid crystals, and at room temperatures in the liquid phase, of some new metalloporphycenes: normal zincporphycene, ZnPCl; Pd(II), and Ni(II) complexes of 2,7,12,17‐tetra‐n‐propylporphycene, PdPC2, PtPC2, and NiPC2, respectively. The triplet state at low temperature is obtained by selective laser excitation and its magnetization response is detected by EPR in the 250 ns time scale. From triplet EPR line shapes and triplet spin polarization directions it is concluded that the zinc cation lies above the molecular plane and the palladium cation fits into the porphycene's cavity. Such a proposed structure implies a strong spin‐orbit interaction in PdPC2, thus resulting in an out‐of‐plane active spin state (z‐axis), whereas that in ZnPCl, having a smaller spin‐orbit interaction, in‐plane (x,y‐axes) are the active spin states. Laser photolysis of the metalloporphycenes gives rise to detectable triplets of ZnPCl, PdPC2 and PtPC2 with triplet lifetimes of 26, 5 and 0.2 µs, respectively. The sensitization experiment, using β‐acetonaphthone as a sensitizer to produce the triplet, results in detectable transients of only ZnPCl and PdPC2 with much longer triplet lifetimes of 85 and 20 µs, respectively. The short triplet lifetime of PtPC2 (and probably that of NiPC2) do not allow for triplet detection with the present sensitizer. However, the latter two metalloporphycenes quench the triplet lifetime of β‐a

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1989.tb04127.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract—Hematoporphyrin derivative(HPD) and other porphyrin samples were excited by 20‐ps 532‐nm laser pulses. Fluorescence was detected using a low‐jitter streak camera. Data were fitted to a sum of exponential decay times on the order of picoseconds. Fluorescence of porphyrins in aqueous solution show various behaviors depending on the hydrophobicity of the porphyrins. The most hydrophilic porphyrins show long decays only(500 ps). Porphyrins intermediate in hydrophobicity have intensity‐dependent fast decays. The most hydrophobic have fast decays (<20 ps). Picosecond fluorescences of mitochondria prepared from rat tumors treatedin vivowith HPD or Photofrin II show an increase in the ratio of fast to slow decays when compared to the injected porphyrins. These results are consistent with the concentration of the more hydrophobic porphyrins in mitochondria in photosensitization treatment. Thus picosecond fluorescence studies of porphyrins may provide a means to obtain photoproperties which differentiate between effective and ineffectivein vivophotose

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1989.tb04128.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract—Eosin derivatives that bind primarily to lipid or protein sites in erythrocyte membranes were studied in solution and as sensitizers of erythrocyte membranes. In 50% ethanol‐water mixtures eosin maleimide (EYMA) and 5‐N‐hexadecanoyl amino eosin (E16) had nearly identical absorption spectra. Higher ethanol concentrations did not change peak absorbances. In the presence of neutral detergent both sensitizers had equivalent absorbance at all ethanol concentrations. In water, EYMA was more effective than E16 at bleaching RNO, probably because of E16 aggregation into micelles, while in ethanol‐water mixtures E16 was slightly more effective at bleaching DPBF, indicating equivalent singlet oxygen generation when the sensitizers are in monomeric form. In water with neutral detergent, azide in the 20 µM .ange inhibited the majority of RNO bleaching with both sensitizers; in 50% ethanol‐water mixtures azide at 1 mM showed a 50% inhibition of DPBF bleaching with both sensitizers. Iodide in the 30 mM range reduced DPBF bleaching by 50% in 50% ethanol‐water mixtures. When matched for amount loaded in erythrocyte membranes these sensitizers were about equally effective at sensitizing induction of cation permeability, assayed as rate of delayed photohemolysis, while E16 was slightly more effective at sensitizing loss of cholinesterase (AchE) activity. The relation of lysis rate to load was somewhat steeper for E16 than EYMA. For both sensitizers lysis rate increased at about the 1.5 power of light dose. Deoxygenation of the reaction media with argon totally blocked detectable photomodification. Ghost membranes made from sensitizer‐treated cells were effective generators of singlet oxygen, assayed by RNO bleaching. However, when mixtures of EYMA‐treated and untreated cells were illuminated together, only the EYMA‐treated cells showed evidence of photomodification. Azide at 5 mM slowed the initial rate of AchE loss by about 75% with E16 and EYMA. Azide partially slowed photohemolysis. Azide decreased RNO bleaching by sensitizer‐treated ghosts as it did in water with detergent micelles. A deuterium oxide solvent increased photohemolysis rate with E16 by 41%, but did not increase photohemolysis rate with EYMA. Deuterium oxide had a positive, but statistically insignificant effect on loss of AchE with both sensitizers. Deuterium oxide following illumination slowed lysis sensitized by both sensitizers more than 50%. Iodide exerted a modest inhibition of photohemolysis and loss of AchE sensitized by E16, but had virtually no influence on sensitization by EYMA. The results in solution indicate that EYMA and E16 have nearly identical photochemical properties when in monomeric form and are minimally sensitive to environmental polarity. The membrane photomodification experiments suggest that both sensitizers actviaintermediates, possibly singlet oxygen, that reach membrane targets through a diffusion path somewhat shielded from agents in the reaction medium, the access being particularl

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1989.tb04129.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract—Irradiation by health lamp (HL) light (280–320 nm) more efficiently induced cell killing and mutation in a radiation sensitive mutant (TW8) ofDictyostelium discoideumas compared with the parental wild‐type strain (NC4). This light as well as a germicidal lamp‐light (254 nm) produced pyrimidine dimers. The dimers were removed from DNA molecules by excision repair in NC4, but more slowly in TW8. It is suggested that pyrimidine dimers are the main DNA damage caused by HL light inD. discoideum, and that this results in cell killing and induced m

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1989.tb04130.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract—The sequence specificity in the photoreaction (365 nm) of 6,4,4′‐trimethylangelicin (TMA) with DNA fragments of thelac Igene ofEscherichia coliwas studied by using DNA sequencing methodology. In order to map the sites of TMA photoaddition, we took advantage of the (3′‐5′) exonuclease activity associated with T4 DNA polymerase, which is blocked by bulky adducts, such as furocoumarin photoadducts. A quantitative analysis of the sites of photoaddition is reported. TMA was demonstrated to photoreact with thymine and, to a lower extent, to cytosine. AT‐rich sequences and I'll sites in a GC context are the most reactive sites towards TMA whereas TA, AT, CA, AC sites are weaker sites with similar reactivity. Cytosines in alternated CG sequences are also targets of TMA photobinding. We observed a less pronounced sequence specificity of TMA than that of other psoralen derivatives already studied (Sage and Moustacchi, 1987; Boyeret al., 1988). A comparison with other furocoumarins 4,4′‐dimethylangelicin (4,4′‐DMA), 4′‐methylangelicin (4′‐MA), angelicin, 4,5′,8‐trimethylpsoralen (TMP) and 8‐methoxypsoralen (8‐MOP) is also reported. The role of flanking sequence and consequently of the local conformation at the various sites of photoaddition is discussed. A preferential orientation of the TMA molecule during the intercalation in the dark is suggested. Hot alkali treatment of TMA‐modified DNA did not reveal any DNA str

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1989.tb04131.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract—Sensitivity of mouse bone marrow and myeloid leukemia cells as well as the sensitivity of human myeloid leukemia cells to UV light was tested. Criteria were thein vivocolony‐forming ability of UV exposed cells and the inhibition of DNA synthesis during post‐irradiation incubation for 24 hin vitro.Mouse bone marrow cells irradiated with a small dose of UV light (5 J/m2) and injected into x‐irradiated animals did not form hemopoietic colonies on the recipients' spleens, and the recipients died. However, mouse leukemia cells, after irradiation with higher doses of UV light, retained the ability to form colonies on the spleens, and all recipient mice died with typical symptoms of leukemia.In vitro, mouse bone marrow cells exhibited high sensitivity to UV light as compared to mouse myeloid leukemia cells. Human leukemia cells were also resistant to UV light, but more sensitive than mouse leukemia cells. These results indicate that myeloid leukemia cells are resistant to UV light as compared with normal bone marro

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1989.tb04132.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY