The Experts below are selected from a list of 201 Experts worldwide ranked by ideXlab platform
John E. Hearst - One of the best experts on this subject based on the ideXlab platform.
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quantitative analysis of dna interstrand cross links and monoadducts formed in human cells induced by Psoralens and uva irradiation
Analytical Chemistry, 2008Co-Authors: Congfang Lai, John E. Hearst, Laurence Corash, Huachuan Cao, Hai Luo, Yinsheng WangAbstract:Upon exposure to UVA light, Psoralens can induce DNA interstrand cross-links (ICLs), which can block DNA replication and transcription. Among the psoralen derivatives, 8-methoxypsoralen (8-MOP) is conventionally applied for psoriasis therapy, and amotosalen S59 is used to inactivate bacterial and viral pathogens in blood components. In addition to the ICL formation, Psoralens also readily form various monoadducts (MAs) with thymidine residues in DNA when exposed to UVA light, and the biological implications for these monoadducts remain unclear. Here, we reported a method that encompassed digestion with a single enzyme (nuclease P1) and LC−MS/MS, for the simultaneous quantification of ICL and MAs induced in human cells exposed with 8-MOP or S59 and UVA light. Our results showed that the yield of ICL induced by S59, which increased from 3.9 to 12.8 lesions/103 nucleotides as the dose of UVA light increased from 0.5 to 10.0 J/cm2, was ∼100 fold more than that induced by 8-MOP. In addition, three and five pro...
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Isolation and characterization of pyrimidine-psoralen-pyrimidine photodiadducts from DNA
Journal of the American Chemical Society, 2002Co-Authors: David B. Kanne, John E. Hearst, Kenneth Straub, Henry RapoportAbstract:The isolation and characterization of pyrimidine-psoralen-pyrimidine photodiadducts from DNA are reported for the first time. For each of the four Psoralens studied, a single pair of diastereomeric thymidine-psoralen-thymidine photodiadducts, each with cis-syn stereochemistry, was found to account for > 90% of the diadducts formed. Additionally, pulse-chase experiments that establish that these photo cross-links are formed by cycloaddition of a second thymidine residue to the 3,4 double bond (pyrone side) of an initially formed 4',5' (furan-side) psoralen-thymidine photomonoadduct have been carried out.
Yinsheng Wang - One of the best experts on this subject based on the ideXlab platform.
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quantitative analysis of dna interstrand cross links and monoadducts formed in human cells induced by Psoralens and uva irradiation
Analytical Chemistry, 2008Co-Authors: Congfang Lai, John E. Hearst, Laurence Corash, Huachuan Cao, Hai Luo, Yinsheng WangAbstract:Upon exposure to UVA light, Psoralens can induce DNA interstrand cross-links (ICLs), which can block DNA replication and transcription. Among the psoralen derivatives, 8-methoxypsoralen (8-MOP) is conventionally applied for psoriasis therapy, and amotosalen S59 is used to inactivate bacterial and viral pathogens in blood components. In addition to the ICL formation, Psoralens also readily form various monoadducts (MAs) with thymidine residues in DNA when exposed to UVA light, and the biological implications for these monoadducts remain unclear. Here, we reported a method that encompassed digestion with a single enzyme (nuclease P1) and LC−MS/MS, for the simultaneous quantification of ICL and MAs induced in human cells exposed with 8-MOP or S59 and UVA light. Our results showed that the yield of ICL induced by S59, which increased from 3.9 to 12.8 lesions/103 nucleotides as the dose of UVA light increased from 0.5 to 10.0 J/cm2, was ∼100 fold more than that induced by 8-MOP. In addition, three and five pro...
Richard R Sinden - One of the best experts on this subject based on the ideXlab platform.
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Probing DNA structure with psoralen in vitro.
Methods in Enzymology, 1992Co-Authors: David W Ussery, Robert W. Hoepfner, Richard R SindenAbstract:Publisher Summary This chapter presents the probing of DNA structure with psoralen in vitro . Psoralens have been widely used as probes of DNA structure, RNA structure, and DNA–protein interaction. Bacterial and eukaryotic cells are permeable to Psoralens that can photobind to DNA inside cells. Psoralen binds preferentially to DNA in cells. The binding of Psoralens to DNA is sensitive to superhelical density, alternate DNA conformations, and protein association. Psoralens initially bind noncovalently to DNA by interacalation into the DNA double helix. The intercalative binding is sufficiently weak that relatively few Psoralens will bind DNA, resulting in little perturbation of the topology and structure of DNA. On irradiation with near-UV light (320-400 nm), an intercalated psoralen can be photobound to an adjacent pyrimidine base, forming a monoadduct. When the adjacent base in the opposite strand is also a pyrimidine, interstrand crosslinks can form in a second photochemical reaction. Cross-links covalently bind the two strands of the double helix together. The number of Psoralens photobound to DNA can be carefully controlled by the incident exposure to UV light. Psoralens bind tightly to proteins and membranes, but the binding is not dependent on irradiation with 360 nm light.
Jeffrey D. Laskin - One of the best experts on this subject based on the ideXlab platform.
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Mechanism of action of Psoralens: isobologram analysis reveals that ultraviolet light potentiation of psoralen action is not additive but synergistic.
Cancer chemotherapy and pharmacology, 1991Co-Authors: Edward J. Yurkow, Jeffrey D. LaskinAbstract:The combination of Psoralens and ultraviolet light (UVA, 320–400 nm), referred to as PUVA, inhibits proliferation of a variety of cell types. In the present studies, we used S-180 cells to investigate the mechanism underlying the antiproliferative actions of PUVA. We found that inhibition of growth of S-180 cells by PUVA was dependent on the concentration of psoralen as well as the dose of UVA light. Neither the Psoralens nor UVA light by themselves inhibited cell growth. Several clinically important psoralen analogs inhibited cell growth. The potent phototoxin 4,5′,8-trimethylpsoralen was the most active psoralen analog tested, followed by 5-methoxypsoralen and 8-methoxypsoralen. The angular furocoumarin, 5-methylangelicin, was the least active inhibitor of growth. Multivariate (isobologram) analysis of the growth-inhibition curves revealed that combinations of Psoralens and UVA light were not simply additive but synergistic. Similar results were observed when inhibition of DNA synthesis was used as an endpoint for the biological effects of PUVA. These studies are the first to demonstrate that Psoralens and UVA light act synergistically. Our results suggest that the synergism between the Psoralens and UVA light may be an important property of PUVA that contributes to its therapeutic efficacy in proliferative diseases.
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Psoralen binding and inhibition of epidermal growth factor binding by psoralen/ultraviolet light (PUVA) in human epithelial cells.
Biochemical pharmacology, 1991Co-Authors: Jeffrey D. Laskin, Edmund LeeAbstract:Abstract The psoralen analogs 8-methoxypsoralen (8-MOP) and 4,5′,8-trimethylpsoralen (TMP), in combination with ultraviolet light (UVA, 320–400 nm), are potent modulators of epidermal cell growth and differentiation and are commonly used in photochemotherapy of psoriasis and vitiligo. We have used KB cells, a human epithelial cell line, to examine the mechanism of action of these compounds. In KB cells, 8-MOP was found to bind to specific, saturable receptor sites. Binding of [ 3 H]-8-MOP to its receptor was inhibited by TMP as well as psoralen. We found that binding of these analogs to the cells followed by UVA light treatment was associated with inhibition of epidermal growth factor (EGF) receptor binding. Inhibition of EGF binding was temperature dependent, occurred immediately following UVA light exposure, and appeared to be due to a decrease in the number of EGF receptors. In KB cells, 125 I-labeled EGF surface receptor binding is followed by its rapid internalization and degradation. We found that photoactivated Psoralens also inhibited internalization of 125 I-EGF, but had no apparent effect on EGF metabolism. These data indicate that the cell surface membrane may be an important target for the photoactivated Psoralens. In addition, since photoactivated Psoralens regulate cell proliferation, the interaction of these compounds with EGF receptor function may underlie their biological activity.
Henry Rapoport - One of the best experts on this subject based on the ideXlab platform.
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Isolation and characterization of pyrimidine-psoralen-pyrimidine photodiadducts from DNA
Journal of the American Chemical Society, 2002Co-Authors: David B. Kanne, John E. Hearst, Kenneth Straub, Henry RapoportAbstract:The isolation and characterization of pyrimidine-psoralen-pyrimidine photodiadducts from DNA are reported for the first time. For each of the four Psoralens studied, a single pair of diastereomeric thymidine-psoralen-thymidine photodiadducts, each with cis-syn stereochemistry, was found to account for > 90% of the diadducts formed. Additionally, pulse-chase experiments that establish that these photo cross-links are formed by cycloaddition of a second thymidine residue to the 3,4 double bond (pyrone side) of an initially formed 4',5' (furan-side) psoralen-thymidine photomonoadduct have been carried out.
