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N. J. De Mol

Bio: N. J. De Mol is an academic researcher from Leiden University. The author has contributed to research in topics: Singlet oxygen & DABCO. The author has an hindex of 9, co-authored 13 publications receiving 408 citations.

Papers
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Journal ArticleDOI
TL;DR: In this article, the formation of singlet molecular oxygen (lO2) by energy transfer from the excited 8-methoxypsoralen (8-MOP) molecule was investigated.
Abstract: — The formation of singlet molecular oxygen (lO2) by energy transfer from the excited 8-meth-oxypsoralen (8-MOP) molecule was investigated. This was done in several ways: (a) In the reaction of irradiated 8-MOP with the 1O2 acceptor 2-methyl-2-pentene, the characteristic oxidation products were identified. (b) The rate of the 8-MOP sensitized photooxidation of 3, 4-dihydroxy phenylalanine (dopa), which appeared to be also a useful 1O2 acceptor, was larger in D2O than in H2O. (c) The β-values for reaction of 1O2with dopa in the presence of 8-MOP or of methylene blue as 1O2 generators were in accordance with each other. The consequences of 1O2 formation by 8-MOP sensitization is discussed for the clinical use of this compound.

78 citations

Journal ArticleDOI
TL;DR: In this paper, the production of singlet oxygen (1O2) by a series of furocoumarins with different skin sensitizing abilities was investigated with methods already proven to be suitable to establish the ability of 8-methoxypsoralen (8-MOP) to generate 1O2.
Abstract: — The production of singlet oxygen (1O2) by a series of furocoumarins with different skin sensitizing abilities has been investigated with methods already proven to be suitable to establish the ability of 8-methoxypsoralen (8-MOP) to generate 1O2. The following compounds: 5-methoxypsoralen (5-MOP), psoralen, 4,5′,8-trimethylpsoralen (TMP) and 5,8–dimethoxypsoralen (5,8–DMOP), are able to generate 1O2 when irradiated with long–wave ultraviolet light. With the photobiologically inactive angelicin no 1O2 production has been found. The relative extent of 1O2 formation has been determined for the various furocoumarins and has been compared with literature data for the skin photosensitizing effect. The observed relation between experimental data on the one side and the literature data on the other side is discussed.

69 citations

Journal ArticleDOI
TL;DR: It can be concluded that 1O2 generated upon UVA irradiation of 8-MOP solutions is probably responsible for part of the observed genetic effects.
Abstract: The possible mutagenic effects induced by singlet oxygen, which is formed during UVA irradiation of bacterial cells pretreated with 8-methoxypsoralen (8-MOP), were investigated. As genetic endpoint, back mutation from arg 56 − to arg + was assayed in strain Escherichia coli K-12/343/113/ uvr B; this system, in preliminary experiments, was rather sensitive to 8-MOP-induced photodynamic effects. To assess the involvement of singlet oxygen ( 1 O 2 ) in the mutation induction process, 2 tests were applied, namely, comparative mutation induction in D 2 O and in H 2 O media (pH 7.0) and quenching of 1 O 2 with 1,4-diazabicyclo[2.2.2]octane (DABCO). When photodynamy was performed with the indicator cells suspended in D 2 O buffer, the mutagenic effect was substantially higher than that obtained with cells suspended in H 2 O buffer; this increase was even more pronounced when the incubation mixtures were thoroughly oxygenated before irradiation. D 2 O itself was not mutagenic under the present experimental conditions. Addition of DABCO in concentrations of 0.1–10 mM to the irradiation mixtures effectively reduced the number of 8-MOP-induced mutant yields by about 40%. DABCO itself had no effect on cell viability or on spontaneous mutation frequency under our experimental conditions. From these 2 sets of results, and from the preliminary findings that the photomutagenic effect of 8-MOP is higher in the uvr B derivative than in the corresponding excision-repair-proficient parent strain, which is in concordance with previous observations in other E coli strains, it can be concluded that 1 O 2 generated upon UVA irradiation of 8-MOP solutions is probably responsible for part of the observed genetic effects.

59 citations

Journal ArticleDOI
TL;DR: In this article, the formation of singlet molecular oxygen (1O2) by sensitization of the furocoumarins 5-methoxypsoralen (5-MOP), 8-methyltoxioxymethylpolysilicon (8-MOPS), and psoralen complexed with DNA was investigated.
Abstract: — The formation of singlet molecular oxygen (1O2) by sensitization of the furocoumarins 5-methoxypsoralen (5-MOP), 8-methoxypsoralen (8-MOP) and psoralen complexed with DNA was investigated. From the results it is concluded that 5-MOP complexed with native DNA is able to generate 1O2, even in a larger extent than 5-MOP free in solution. Also, with 8-MOP and especially with psoralen, 1O2 formation by the complexed compound could be observed. The 1O2 formation sensitized by covalently bound furocoumarin was demonstrated with psoralen as a model compound. 4′,5′-Dihydropsoralen, a model compound for the UVA light absorbing 4′,5’monoadducts of furocoumarins to DNA, is also able to generate 1O2.

56 citations

Journal ArticleDOI
TL;DR: The irreversible binding of chlorpromazine radical cation (CPZ+.) and photoactivated chlor Promazine ( CPZ) to calf thymus DNA in vitro and bacterial macromolecules in intact bacterium cells was investigated and the consequences of covalent binding for the cytotoxicity and genotoxicity of CPZ+.

39 citations


Cited by
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Journal ArticleDOI
TL;DR: A review with 310 references summarizes the current knowledge of the photochemical behavior of pharmaceuticals and highlights the use of the fundamental photochemistry and phototoxicity literature to help understand and predict the aquatic fate of pharmaceutical drugs.
Abstract: A review with 310 references. Photochemical degradation is likely to be an important loss mechanism for many pharmaceutical pollutants in surface waters. This review summarizes the current knowledge of the photochemical behavior of pharmaceuticals and highlights the use of the fundamental photochemistry and phototoxicity literature to help understand and predict the aquatic fate of pharmaceuticals. Naproxen and diclofenac are shown to exemplify the idea that photochemical behavior obtained from fundamental photochemistry studies can be related to environmental conditions. There are, however, numerous compounds that have been found in environmental matrices for which no photochemistry data relatable to environmental conditions are available. It will be necessary to combine the results available in the large body of fundamental photochemistry and phototoxicity literature with laboratory and field experiments designed to determine direct and indirect photolysis rates and to identify photoproducts. This course will lead to a thorough understanding of the role of photodegradation on the fate and impact of pharmaceutical pollutants.

424 citations

Journal ArticleDOI
TL;DR: In this paper, a review of the generation, occurrence and action of singlet oxygen in plant tissue is presented, focusing on its formation from triplet sensitizers and its reactivity with molecules of biological importance such as lipids and amino acids.

336 citations

BookDOI
01 Jan 1982
TL;DR: Presented at the 7th Annual Meeting of the American Society for Photobiology, June 24-28, Pacific Grove, California.
Abstract: presented at the 7th Annual Meeting of the American Society for Photobiology, June 24-28, Pacific Grove, California. Programs and Abstracts, p. 175. 53. Schleider, N. R., Moskowitz, R. S., Cort, D. H., et a!. (1979): Effects of emollients on ultraviolet-radiation-induced erythema of the skin. Arch. Dermato!' 115: 1188-1191. 54. Frost, P., Horwitz, S. N., Caputo, R. V., et a!. (1979): Tar gel-phototherapy for psoriasis. Arch. DermalOl. 115:840-846. 55. Kaidbey, K. H., Grove, G. L., and Kligman, A. M. (1979): The influence of longwave ultraviolet radiation on sunburn cell production by UVB. J. Invest. Dermato!' 73:243-245. 56. Gschnait, F., Brenner, W., and Wolff, K. (1978): Photoprotective effect of a psoralen-UVAinduced tan. Arch. Dermatol. Res. 268: 181-188. 57. Kaidbey, K. H., and Kligman, A. M. (1979): The acute effects of longwave ultraviolet radiation on human skin. 1. Invest. Dermatol. 72: 253-256. 58. Parrish, J. A., Zaynoun, S., and Anderson, R. R. (1981): Cumulative effects of repeated subthreshold doses of ultraviolet radiation. J. Invest. Dermatol. 76:352-355. 59. Everett, M. A., Daffer, E., and Coffey, C. M. (1961): Coal tar and ultraviolet light. Arch. DermalOl. 84:473-476. 60. Ellis, C. C. (1948): The treatment of psoriasis with liquor carbonis detergens. J. Invest. Dermatol. 10:455. 61. Ingram, J. T. (1953): The approach to psoriasis. Br. Med. J. 2:591-594. Phototherapy of Skin Diseases 531 62. Comaish, S. (1965): Ingram method of treating psoriasis. Arch. Dermato!. 92:56-58. 63. Beierdorffer, H., and Wiskemann, A. (1978): Kombinierte Therapie der Psoriasis mit einem aromatischen Retinoid (RO 10-9359) und UYB-Bestrahlungen. Aktue!. Dermato!. 4: 183-187. 64. Steigleder, G. K., Orfanos, C. E., and Pullmann, H. (1978): Retinoid-SUP-Therapie der Psoriasis. Z. Hautkr. 54: 19-23. 65. Momtaz-T., K., and Parrish, J. A. (1981): Combination UYB and PUY A in the treatment of psoriasis. J. Invest. Dermato!' 76: 303. 66. Walter, J. F., Stoughton, R. B., and DeQuoy, P. R. (1978): Suppression of epidermal and proliferation by ultraviolet light, coal tar and anthralin. Br. J. Dermato!' 99:89-96. 67. Stoughton, R. B., DeQuoy, P., and Walter, J. F. (1978): Crude coal tar plus near ultraviolet light suppresses DNA synthesis in epidermis. Arch. Dermato!' 114:43-45. 68. Cecht, T., Pathak, M. A., and Biswas, R. K. (1979): An electron microscopic study of the photochemical cross-linking of DNA in guinea pig epidermis by psoralen derivatives. Biochim. Biophys. Acta 562:342-360. 69. Pathak, M. A., and Biswas, R. K. (1977): Skin photosensitization and DNA cross-linking ability of photochemotherapeutic agents (Abstract). J. Invest. Dermato!. 68:236. 70. Stern, R. S., Zierler, S., and Parrish, J. A. (1980): Skin carcinoma in patients with psoriasis treated with topical tar and artificial radiation. Lancet 1:732-735.

320 citations

Journal Article
TL;DR: The augmentation of cell death in the presence of D(2)O and the protection afforded by quenchers and scavengers of singlet oxygen, indicates that the generation of Singlet oxygen may be involved in the mechanisms leading to the death of A2E-containing RPE cells after blue light illumination.
Abstract: Purpose The lipofuscin fluorophore A2E is known to be an initiator of blue-light-induced apoptosis in retinal pigment epithelial cells (RPE) The purpose of this study was to evaluate the role of oxidative mechanisms in mediating the cellular damage Methods Human RPE (ARPE-19) cells that had accumulated A2E were exposed to blue light in the presence and absence of oxygen, and nonviable cells were quantified Potential suppressors (histidine, azide, 1,4-diazabicyclooctane [DABCO], and 1,3-dimethyl-2-thiourea [DMTU]) and enhancers (deuterium oxide [D(2)O] and 3-aminotriazole [3-AT]) of oxidative damage, were also screened for their ability to modulate the frequency of nonviable cells A2E in PBS, with and without an oxygen-depleter or singlet-oxygen quencher and A2E-laden RPE, were exposed to 430-nm light and examined by reversed-phase high performance liquid chromatography (HPLC) and fast atom bombardment mass spectrometry (FAB-MS) Results The death of blue-light-illuminated A2E-laden RPE was blocked in oxygen-depleted media When A2E-laden RPE were transferred to D(2)O-based media and then irradiated (480 nm), the number of nonviable cells was increased, whereas the latter was decreased in the presence of histidine, DABCO, and azide Conversely, no affect was observed with 3-AT and DMTU When A2E, in either acellular or cellular environments, was irradiated at 430 nm, FAB-MS revealed the generation of a series of higher molecular mass derivatives of A2E The sizes of these species increased by increments of mass 16 The generation of these photo-products was accompanied by the consumption of A2E, the latter being diminished, however, when illumination was performed after oxygen depletion and in the presence of a singlet-oxygen quencher Conclusions The augmentation of cell death in the presence of D(2)O and the protection afforded by quenchers and scavengers of singlet oxygen, indicates that the generation of singlet oxygen may be involved in the mechanisms leading to the death of A2E-containing RPE cells after blue light illumination The finding that irradiation also produces oxygen-dependent photochemical changes in A2E, indicates that the effects of singlet oxygen may be mediated either directly or through the generation of reactive photo-products of A2E

289 citations