bluuebunny/crossref_metadata_2025_split huggingface dataset:
Photodynamic Effects of Hypericin on Lipid Peroxidation and Antioxidant Status in Melanoma Cells
Authors: Hadjur Christophe , Richard Marie‐Jeanne , Parat Marie‐Odile , Jardon Pierre , Favier Alain 
Published: January 2008

AbstractPhotodynamic‐induced cytotoxicity by hypericin (HYP) was studied on three human melanoma cell lines: one pigmented cell line (G361) and two amelanotic cell lines (M18 and M6). No significant variation in the rate of uptake and in the maximum level of HYP incorporation for the different cells was observed. In the dark, no cytotoxicity was observed in the range0–10−6M HYP for the three cell lines. Amelanotic cells were found to be more sensitive than pigmented cells to irradiation of HYP with visible light (Λ > 590 nm). In addition, for the three cell lines HYP‐induced photocytotoxicity was found to be drug‐dose and light‐dose dependent. Under the conditions used, thiobarbituric acid‐reacting substances (TBARs) were significantly increased in amelanotic cells after irradiation (P < 0.0001). By contrast, the amount of TBARS remained unchanged in pigmented cells. Antioxidant defenses including enzymes and glutathione (GSH) were assayed before and after HYP photosensitization. Significantly increased total SOD activity was observed after photosensitization for amelanotic cells (P < 0.05), while glutathione peroxidase (GSHPx) and catalase (Cat) activities but also GSH levels were significantly decreased (P < 0.01). In pigmented cells a significantly increased Cat activity was found (P < 0.05), whereas GSHPx was unaffected after irradiation. It can be inferred that (a) HYP may be an effective PDT agent for melanoma and (b) there is a relationship between melanin content and sensitivity to HYP phototoxicity in human melanoma cells.
Liposome‐Mediated Delivery of Photosensitizers: Localization of Zinc (11)‐Phthalocyanine within Implanted Tumors after Intravenous Administration
Authors: Love W. G. , Duk S. , Biolo R. , Jori G. , Taylor P. W. 
Published: January 2008

ABSTRACTCGP55847, liposomal zinc(II)‐phthalocyanine (Zn‐Pc), was administered by the intravenous route to Swiss mice bearing intramuscularly implanted Ehrlich carcinomas or to C57BL6 mice bearing subcutaneously implanted B16 melanomas. Tumors were removed 3 h or 24 h after dosing and the intratumoral distribution determined by fluorescence microscopy. Localization of the photosensi‐tizer occurred more rapidly in the Ehrlich carcinoma than in the B16 melanoma; this difference in photosen‐sitizer uptake may be related to a higher degree of vas‐cularization of the carcinoma. The photosensitizer was found in association with blood vessels at 3 h but not 24 h after dosing and appeared to have a greater affinity for areas of tissue necrosis within the tumor compared to viable tumor tissue. Little or no Zn‐Pc was detected in the muscle tissue invaded by the Ehrlich carcinoma and was associated with membranes and the cytosol, but not the nucleus, of cells in both tumors.
The Photochemistry of the Retinoids as Studied by Steady‐State and Pulsed Methods
Authors: Dillon James , Gaillard Elizabeth R. , Bilski Piotr , Chignell Colin F. , Reszka Krzysztof J. 
Published: January 2008

ABSTRACTThe retina and retinal pigment epithelium contain a number of retinoids in a metabolic pathway that eventually forms the visual pigments. This study investigates the photochemistry of those retinoids that may contribute to light‐induced damage to the retina. These include retinal (RAL), retinol (ROL), retinylpalmitate (ROLpal) and the protonated Schiff‐base of retinal (RAL.,). Their photochemistry was followed by both EPR spin‐trapping techniques and the direct detection of singlet oxygen via its luminescence at 1270 nm. Irradiation (>300 nm) of RAL, ROL in methanol (MeOH) or RALpal in dimeth‐ylformamide, produces free radicals from both solvents. Illumination of RAL., in MeOH containing NADH with light above 400 nm (and even above 455 nm) generates the superoxide radical. We also determined that the quantum yields for singlet oxygen sensitization by RAL, ROL or RALpal in MeOH are 0.05, 0.03 and 4.01, respectively. These values are at least 75% less than those previously found using chemical methods. These observations indicate that a major photochemical process for these retinoids may be an electron (or hydrogen) process that will lead to radical products, and that the singlet oxygen mechanism is of relatively minor importance in protic solvents. These results may explain the action spectra obtained from light‐induced damage to the retina.
Isolation and Partial Characterization of a Novel Psoralen‐Tyrosine Photoconjugate from a Photoreaction of Psoralen with a Natural Protein
Authors: Sastry Srinivas S. 
Published: January 2008

ABSTRACTThe photoreaction of psoralens with DNA is a well‐characterized reaction. However, the photoreactions of psoralens with proteins is not very well understood. Our objective was to isolate an amino acid‐psoralen photochemical adduct. We photoreacted 8‐methoxypsoralen (8‐MOP) with T7 RNA polymerase, a protein that carries out the fundamental biological process of transcription. Amino acid composition analysis of the photoreacted polymerase revealed that tyrosines quantitatively reacted with 8‐MOP. From the acid hydrolysates of the photo‐conjugated T7 RNA polymerase, an 8‐MOP‐tyr adduct was partially purified by HPLC. The purified 8‐MOP‐tyr adduct and related parent compounds were analyzed by UV‐visible absorption, fluorescence and mass spectroscopy. Excitation/absorption spectra suggested that the pyrone of the original 8‐MOP was modified in the isolated photoadduct, and that the adduct probably contained a benzofuran. Chemical ionization mass spectrometry was consistent with the photoaddition of tyr to 8‐MOP with a conservation of the overall mass (±1 atomic mass units). As far as we know, this work represents the first instance of isolation and partial characterization of an amino acid‐psoralen photoadduct.
Recent Trends in the Evaluation of Photochemical Insertion Characteristics of Heterobifunctional Perfluoroaryl Azide Chelating Agents: Biochemical Implications in Nuclear Medicine
Authors: Pandurangi Raghoottama S. , Karra Srinivasa R. , Kuntz Robert R. , Volkert Wynn A. 
Published: January 2008

AbstractAchieving high efficiency covalent attachment of molecular probes to biomolecules by photolabeling techniques remains an elusive goal of chemists and biologists. Developments in the understanding of the fundamental photochemistry of perfluoroaryl azides suggest a new means of attaching diagnostic and therapeutic radionuclei to proteins and antibodies through heterobifunctional chelating agents containing a photoactive terminus. Such an approach requires establishment of the coordination chemistry of ligating systems, appropriate molecular design of the photolabel, analytical method development for critical analysis of photolabeled products and retention of immunoreactivity of antibodies in the postlabeling stage. In this review, we summarize recent developments in photolabeling technology and discuss new challenges for application of the technology in the field of nuclear medicine.
Formation and Processing of UV Photoproducts: Effects of DNA Sequence and Chromatin Environment
Authors: Pfeifer Gerd P. 
Published: January 2008

AbstractCyclobutane pyrimidine dimers and (6–4) photoproducts are the two major classes of lesions produced in DNA by UVB and UVC irradiation. Their distribution along genes is nucleotide sequence‐dependent. In vivo, the frequency of these lesions at specific sites is modulated by nucleosomes and other DNA binding proteins. Repair of UV photoproducts is dependent on the transcriptional status of the sequences to be repaired and on the chromatin environment. The formation of DNA photolesions by UV light is responsible for the induction of mutations and the development of skin cancer. To understand the mechanisms of UV mutagenesis, it is important to know how these lesions are formed, by which cellular pathways they are repaired and how they are dealt with by DNA polymerases.
Reactivity of Singlet Oxygen Toward Proteins: The Effect of Structure in Basic Pancreatic Trypsin Inhibitor and in Ribonuclease A
Authors: Michaeli Albert , Feitelson Jehuda 
Published: January 2008

AbstractThe reactions of singlet oxygen, 1O2, with large peptides have been described previously. It was found that even in these systems, which in their native form are generally not supposed to possess a stable structure in solution, the polypeptide does impede the access of 1O2 to the amino acids that react readily with 1O2. Here we describe the 102 reaction with two proteins of well‐defined structure. The quenching of 1O2 by bovine pancreatic trypsin inhibitor (BPTI) and by ribonuclease A (RNase A) was compared to that of a solution at the same concentration as those of its constituent amino acids that react readily with 1O2. The proteins were studied in their native form, when partly denatured by splitting their S‐S bonds and when fully denatured. It was found that while in the native form the quenching rate constant was seven times lower in BPTI (2.2 vs 15.2 times 107WM‐1 s‐1) and three times lower in RNase A (11.0 vs 32 times 107M‐l s‐1) than in a mixture of its constituent amino acid residues, it increased upon denaturation reaching in the fully denatured state the value of the corresponding amino acid mixture. More striking is the effect of the protein structure when comparing the fraction of the encounters between 1O2 and protein, which cause damage to the protein, as reflected in the decrease of its biological activity. This decrease is assumed to be due to the chemical (oxidative) reactions of 1O2 in the protein. In the exceptionally stable BPTI the fraction of such encounters was 0.05 and in RNase A it was 0.2, whereas for the amino acid tryptophan in solution, 0.7 of the collisions with 1O2 led to a chemical reaction.
Time and Dose Dependence of Acceptance of UV‐lnduced Syngeneic Tumor Implants in Chronically UV‐Exposed Hairless Mice
Authors: Sontag Yvonne , Steerenberg Peter , Garssen Johan , van Loveren Henk , van der Leun Jan C. , van Vloten Willem A. , de Gruijl Frank R. 
Published: January 2008

AbstractThe kinetics of skin cancer induction by UV radiation has been extensively studied in hairless mice and described by Weibull statistics in which the time till 63% of the mice bear tumors is a primary parameter. However, the kinetics of the associated immunosuppression remained to be determined. To this end, we implanted a syngeneic UV‐induced skin carcinoma cell line (T51/6.53) in the ventral skin of HRA/SKH hairless mice after various periods of daily dorsal UV exposure, either 150 or 75 mj/cm2 per day UV from F40 sunlamps (regimens that when continued yield 63% of the mice with 1 mm tumors in 11.5 or 16.2 weeks, respectively). Both exposure regimens achieved a 100% acceptance (after 7 and 16 weeks, respectively). The implants failed to grow in all unirradiated control mice, but the percentage of mice in which the implants grew increased with the UV treatment time and dose. The estimated times to 63% implant acceptance were 4.3 ± 0.8 and 8.2 ± 0.8 weeks for the high and low daily doses, respectively. As reported earlier for shaved haired mice, there appears to be a straight reciprocity between daily UV dose and the time to tumor acceptance, i.e. the latter fully depends on the cumulative UV dose, whereas the tumor induction does not. The latter probably also depends on a pure elapse of time, i.e. U V‐independent processes. A further analysis of the Weibull description indicates that immunosuppression toward the tumor requires fewer UV‐driven steps than tumor induction.
Photoreaction of New Psoralen Analogs with DNA: Sequence and Mutation Specificity in the Escherichia coli lacZ Gene
Authors: Collet Marianne , Sage Evelyne , Piette Jacques 
Published: January 2008

AbstractNew thio‐ and seleno‐analogs of psoralen were synthesized and analyzed for their photoreactivity toward DNA. Using oligonucleotides of denned sequence, we first showed that these derivatives predominantly generated interstrand crosslinks at 5′‐TpA sites. We also observed a surprisingly high reactivity of 7H‐thiopyrano[3,2‐f][l]benzofuran‐7‐one (PSO[0‐S]) with the BamHl and PstI oligomers, giving rise to the formation of crosslinks at 5′‐ApT sites and of the thymidine‐psoralen‐cytosine type. Next, the sequence specificity in the photochemical binding of all the compounds was investigated in two DNA fragments encompassing the lacZ gene of Escherichia coli, using the T4 DNA polymerase sequencing methodology. Resulting maps demonstrated that thio‐and seleno‐analogs of psoralen preferentially photoreact‐ed with thymine and cytosine residues. The AT‐rich sequences proved to be particularly reactive sites as did adjacent thymines, especially at C‐surrounding residues. Likewise, photoaddition at cytosines in CA/AC context was observed. It was highly significant that all of the derivatives exhibited similar sequence specificities with only minor differences. However, PSO(O‐S) differed from the other heteropsoralens. Photoadducts occurred with a higher frequency at AC and CA dinucleotides, and new sites were detected. A comparison with 8‐methoxypsor‐alen photobinding is also reported. Finally, the mutagenic consequences of photoadducts induced in M13mp19 DNA by PSO(O‐S) were determined in a forward system that detects all classes of mutagenic events. The high phototoxicity exhibited by PSO(O‐S) could be attributed to crosslinks, and the comparison of the observed mutational specificity with the photoadduct distribution within the same gene showed that mutations were targeted at potential monoadduct sites where photolesions were detected in our footprinting experiments
An Assay for the Quantitation of Photofrin in Tissues and Fluids
Authors: Bellnier David A. , Greco William R. , Parsons John C. , Oseroff Allan R. , Kuebler Alex , Dougherty Thomas J. 
Published: January 2008

Abstract A method for determining the concentration of Photofrin in tissues and biological fluids was developed. The procedure is based on the dissolution of biological material with Solvable a commercially available tissue so‐lubilizer, followed by porphyrin‐specific fluorescence detection and measurement. It was found necessary to use a quadratic standard curve for the estimation of unknown Photofrin concentrations. While this method is limited to compounds that are stable in strong base, it has the advantages of being sensitive, rapid and low cost.
Chronically Ultraviolet‐exposed Human Skin Shows a Higher Mutation Frequency of Mitochondrial DNA as Compared to Unexposed Skin and the Hematopoietic System
Authors: Berneburg Mark , Gattermann Norbert , Stege Helger , Grewe Markus , Vogelsang Kathrin , Ruzicka Thomas , Krutmann Jean 
Published: January 2008

Abstract Normal ageing processes are associated with an accumulation of mutations within the mitochondrial (mt) DNA. The most frequent mutation is a 4977 base pair (bp) deletion known as common deletion. In order to test the hypothesis that chronically sun‐exposed skin is characterized by an increased mutation frequency of mtDNA, the mutation frequency of the common deletion between skin and another replicating tissue (the hematopoietic system) and chronically sun‐exposed versus sun‐protected skin was compared in the same individuals. This was done by comparing the amount of mutated mtDNA molecules with the whole mitochondrial genome in the same specimen with a semiquantitative polymerase chain reation method, thus allowing direct comparison of different tissues. In all skin specimens the common deletion could be observed. In contrast only 3 of 10 blood samples revealed detectable amounts of the common deletion. Comparison of sun‐exposed versus sun‐protected skin exhibited a higher content of the common deletion in sun‐exposed skin in 7 of 10 individuals. Additionally, a hitherto undescribed mtDNA mutation was detected exclusively in human skin. These studies indicate that exposure of human skin to solar radiation leads to an accumulation of mtDNA mutations, possibly via oxidative damage, which may play an important role in photoageing.
An Unexpected Spectrum of p53 Mutations from Squamous Cell Carcinomas in Psoriasis Patients Treated with PUVA
Authors: Wang Xiao Mei , McNiff Jennifer Madison , Klump Vincent , Asgari Maryam , Gasparro Francis P. 
Published: January 2008

AbstractPhotochemotherapy employing 8‐methoxypsoralen and long‐wavelength ultraviolet radiation (UVA, 320‐400 nm) is widely used in the treatment of psoriasis. The pho‐toactivation of psoralens in skin cells leads to formation of DNA photoadducts which may be responsible, at least in part, for the efficacy of these photochemotherapies. However, mutations arising from these adducts may also lead to the well‐characterized increased incidence of squamous cell carcinoma. Mutations in the p53 tumor suppressor gene have been detected in many human cancers. To determine whether p53 mutations occur in squamous cell carcinomas in PUVA patients, PCR was used to amplify the exons (5‐9) in which other studies have found a high frequency of point mutations. Gel electrophoresis was used to detect single‐strand conformational polymorphisms. Aberrantly migrating bands were excised, reamplined and sequenced. Thirty‐four specimens from 10 patients were examined. Specimens from one patient who had received no phototherapy as well as from normal controls were also analyzed. Five of the 10 patients showed at least one p53 mutation. In contrast to previously reported psoralen‐induced p53 mutations in mice, the expected psoralen type mutations at alternating AT sites were not detected. All but two of the altered sequences occurred at dipyrimidine sites which is typical of solar type mutations. Two C→T mutations and two dipyrimidine mutations (CC→TT) were found. Other mutations included: C→G, G→T, C→A and an 18 bp deletion. A review of therapeutic history of these patients showed that some had also received UVB phototherapy. Furthermore, because sunlight is thought to be beneficial for psoriasis, nontherapeutic, casual UVB exposure cannot be excluded. Our observations suggest that the SCC may have arisen from the solar mutations and that PUVA may enhance tumor progression or immune suppression
Photobiological Properties of 1′‐Thieno‐4,6,4′‐trimethylangelicin
Authors: Bordin F. , Marzano C. , Baccichetti F. , Carlassare F. , Vedaldi D. , Falcomer S. , Lora S. , Rodighiero P. 
Published: January 2008

AbstractSome photobiological properties of l'‐thieno‐4,6,4′‐tri‐methylangelicin (TTMA), a new isoster of 4,6,4′‐trimeth‐ylangelicin (TMA) were studied in comparison with the parent compound. The TTMA absorbs UVA light and photobinds in vitro to DNA more efficiently than TMA; however, in Ehrlich cells in vivo TTMA linked to DNA to a lesser extent than the parent compound. In general, the formation of damage into DNA is in line with this last result: In fact, TTMA and TMA form equivalent amounts of interstrand cross‐links (ISC) both in vitro in linearized PM2 DNA and in vivo in HeLa cells. In this system TTMA induces DNA‐protein cross‐links (DPC) more efficiently than TMA; on the contrary, no significant amounts of single‐strand breaks were detected with both compounds. The antiproliferative activity of TTMA is consistent with these results, being only slightly more pronounced than that of TMA. Experiments carried out using double irradiation demonstrated that these drugs are capable of inducing antiproliferative effects by bi‐photonic reactions, including the formation of both ISC and DPC. Thus, replacement of the oxygen atom by a sulfur increases the UV absorption of the drug and its capacity to photobind to DNA in vitro but does not yield a comparable enhancement of its photosensitizing properties in vivo; this might be due to various reasons, for instance to an increase in the lipophilic character that could modify the behavior in vivo.
Structural Volume Changes upon Photoisomerization of the Bilirubin‐Albumin Complex: A Laser‐Induced Optoacoustic Study‡
Authors: Williams Rene M. , McDonagh Antony F. , Braslavsky Silvia E. 
Published: January 2008

AbstractThe Z → E photoisomerization of the 1:1 complexes of human serum albumin (HSA) and several bilirubins (BR‐IXα, ‐IIIα, meso‐IXα and a mixture of ‐IXα, ‐IIIα and XHIα) affords in every case an almost negligible structural volume change (δVR = 0) within detection limits (i e. less than2–4 cm3/mol for this isomerization with very low quantum yield) as determined by laser‐induced optoacoustic spectroscopy. Based on previous model studies of photoisomerizations in aqueous environment, this negligible small change is interpreted as indicating that the part of the molecule undergoing photoisomerization is not exposed to water but is located in a hydrophobic protein cavity that shields the molecule from the aqueous medium. The BR‐protein interaction within this cavity seems to be very loose in view of the small structural volume change observed. The energy difference between the Z and E isomers of the BR‐HSA complexes was estimated to be less than 4 kJ/mol, probably close to zero (ΔH = 0).
Carotenohematoporphyrins as Tumor‐Imaging Dyes. Synthesis and In Vitro Photophysical Characterization*
Authors: Tatman Dereck , Liddell Paul A. , Moore Thomas A. , Gust Devens , Moore Ana L. 
Published: January 2008

AbstractMultichromophoric dyes for use in tumor imaging have been synthesized and photophysically characterized. Structurally, these dyes are dyads and triads that consist of one or two carotenoid polyenes covalently attached to hematoporphyrin (HP) or hematoporphyrin dimethyl ester (HPDME) moieties via ester linkages. The ground‐state absorption of each compound shows that the electronic interaction between the chromophores is small. The fluorescence quantum yield for the dyad monocar‐oteno‐ HPDME is 0.033 and the dicaroteno‐HPDME triads have yields between 0.016 and 0.007, all of which are reduced with respect to the parent compound HPDME (0.09). Global analysis of the transient fluorescence decays of the dyads and triads requires two exponential components (˜5–6ns and ˜1–2ns) to fit the data, while a single exponential component with a lifetime of 9.3 ns describes the decay data of the parent HPDME. Possible mechanisms for the observed porphyrin fluorescence quenching by the nearby carotenoid are discussed. Nanosecond transient absorption reveals a carotene triplet with maximum absorption at 560 nm and a 5.0 μs lifetime. No transient was detected at 450 nm, indicating rapid (10 ns) triplet energy transfer from the hematoporphyrin to the carotenoid moieties in fluid as well as in rigid media. The yield of triplet energy transfer from the porphyrin to the carotenoid moiety is unity. Singlet oxygen, O2(1δg), studies support the transient absorption data, as none of these compounds is capable of sensitizing O2(1δg). Liposome vesicles were used to study the photophysical characteristics of the dyes in phospholipid membranes. Singlet oxygen was not sensitized by the dyads and triads in liposomes. Transient absorption measurements suggest that the triads are substantially aggregated within the phospholipid bilayer, whereas aggregation in the dyads is less severe.