Search PubMed⌕ Search

Biomedical subjects

J Cadet

Publications and source records attributed to J Cadet.

At least 163 records · Page 9Linked to original sources
PubMed1986

Chemical structure of 3-carbethoxypsoralen-DNA photoadducts.

The enzymatic digest from salmon sperm DNA photochemically modified by the monofunctional 3-carbethoxypsoralen was analyzed by high-performance liquid chromatography. The modified nucleosides extracted from DNA were compared with model compounds obtained from irradiation in the dry state of mixtures of 3-carbethoxypsoralen with 2'-deoxyribonucleosides whose chemical structures had previously been characterized. The main photoadducts formed in DNA are two cis-syn diastereoisomers formed via a C4-cycloaddition reaction involving the 4', 5' double bond of 3-carbethoxypsoralen and the 5,6 double bond of 2'-deoxythymidine. Among them, the most polar one accounts for 72%. Under the same conditions, photoadducts formed between 3-carbethoxypsoralen and 2'deoxycytidine account for less than 1%.

Chemical Phenomena↗
PubMed1986

Photosensitized reactions of nucleic acids.

The main effects of near-ultraviolet and visible light on cellular DNA are reviewed with emphasis on base lesions, oligonucleotide single-strand breaks and DNA-protein cross-links. Model system photosensitization reactions of DNA are also discussed. This includes photodynamic effects, menadione-mediated photooxidation, photoionization of antibiotics, the photochemistry of 5-halogenopyrimidines and urocanic acid.

4-Aminobenzoic Acid↗
PubMed1986

Sensitized photo-oxidation of thymidine by 2-methyl-1,4-naphthoquinone. Characterization of the stable photoproducts.

The near ultraviolet photolysis of an aerated aqueous solution of thymidine containing 2-methyl-1,4-naphthoquinone gives rise to two main classes of photoproducts as a result of the initial formation of a pyrimidine radical cation. These photo-oxidation products have been separated by high performance liquid chromatography and further characterized by various spectroscopic techniques including fast atom bombardment mass spectrometry and high field 1H and 13C nuclear magnetic resonance analysis. This photoreaction constitutes an excellent model to study the chemical properties of the thymidine radical cation which is expected to be one of the primary consequences of the direct effects of ionizing radiation.

Oxidation-Reduction↗
PubMed1986

Isolation and characterization of psoralen photoadducts to DNA and related model compounds.

The main products of the photoreaction of 3-carbethoxypsoralen and 8-methoxypsoralen with 2'-deoxyribonucleosides have been isolated and characterized by various spectroscopic measurements involving proton nuclear magnetic resonance and mass spectrometry (fast atom bombardment and 252Cf plasma desorption techniques). Near ultraviolet photolysis of frozen aqueous solutions of thymidine containing 3-carbethoxypsoralen gives rise to two furan-side photocycloadducts having cis-syn stereochemistry. The corresponding thymine mean value of 3-carbethoxy-psoralen monoadduct has been shown to be the major photoproduct in DNA. The main cis-syn diastereoisomeric [2+2] photocycloadducts which arise from the photoreaction of 8-methoxypsoralen and thymidine in frozen aqueous solutions were shown to involve either the 4',5' furan ring or the 3,4 pyrone moiety and the 5,6-pyrimidine bond. Photobinding of 8-methoxypsoralen to 2'-deoxyadenosine also occurs, with covalent bond formation between carbon 3 or 4 of the pyrone ring and the sugar moiety of the nucleoside.

DNA↗
PubMed1985

Quantitative determination of the 5-(hydroxymethyl)uracil moiety in the DNA of gamma-irradiated cells.

5-(Hydroxymethyl)uracil (HMUra) is a chemically stable derivative of thymine formed through the action of ionizing radiation which we previously identified in the DNA of gamma-irradiated HeLa cells [Teebor, G. W., Frenkel, K., & Goldstein, M. S. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 318-321]. In this report, we determine whether HMUra can be used as a marker of exposure of DNA to ionizing radiation. Dose-response curves for its formation in [3H]thymidine-labeled DNA were constructed by exposing the DNA to increasing amounts of gamma-radiation and measuring the HMUra content. DNA was irradiated both in solution and in intact cells. HMUra was identified as the 2'-deoxyribonucleoside 5-(hydroxymethyl)-2'-deoxyuridine (HMdU) by subjecting the irradiated DNA to enzymatic digestion and analyzing the mixture of 2'-deoxyribonucleosides by high-pressure liquid chromatography. The identity of the radiogenically formed HMdU was confirmed by acetylation and the structure of the acetyl derivative obtained by mass and nuclear magnetic resonance spectroscopies. At two different DNA concentrations in solution, the same number of thymidine moieties were converted to HMdU, indicating that within this range of concentration the formation of HMdU was mediated through the indirect action of ionizing radiation. Equal amounts of HMdU were formed in single- and double-stranded DNA at each radiation dose, indicating that DNA conformation did not affect HMdU formation. Surprisingly, the G value (number of HMdU molecules formed/100 eV) was higher in irradiated cellular DNA than in DNA irradiated in solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗
PubMed1985

Radiation-induced decomposition of the purine bases within DNA and related model compounds.

This survey focuses on recent developments in the radiation chemistry of purine bases in nucleic acids and related model compounds. Both direct and indirect effects of ionizing radiation are investigated with special emphasis on the structural characterization of the final decomposition products of nucleic acid components. Available assays for monitoring radiation-induced base lesions are critically reviewed.

Adenine↗
PubMed1983

Rapid quantitation of ultraviolet-induced thymine-containing dimers in human cell DNA by reversed-phase high-performance liquid chromatography.

Rapid and efficient separation of all three types of cyclobutyl pyrimidine dimer (Pyr mean value of Pyr) species induced in cellular DNA by far-ultraviolet (UV) light (chiefly 254 nm) has been achieved by reversed-phase high-performance liquid chromatography using octadecylsilyl stationary phases. The order of elution is: (Ura mean value of Ura) less than (Ura mean value of Thy) less than (Thy mean value of Thy) less than Thy. The determination of Pyr mean value of Pyr species in DNA from UV-irradiated, [3H]thymidine-labelled human skin fibroblasts in tissue culture is demonstrated for far-UV fluences as low as 10 J/m2. The ability to measure specifically individual dimer types allowed demonstration of comparable kinetics of repair for two labelled dimer species (Ura mean value of Thy and Thy mean value of Thy).

Cells, Cultured↗
PubMed1982

Uracil-DNA glycosylase. Purification and properties of uracil-DNA glycosylase from Micrococcus luteus.

A uracil-DNA-glycosylase from Micrococcus luteus has been purified more than 3,000-fold. The enzyme preparation appears homogeneous, according to the results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It is devoid of nonspecific endonucleases, specific endonucleases for apurinic and apyrimidinic sites, 3-methyladenine or 7-methylguanine-DNA-glycosylases. It behaves as a monomer protein of 19,400 daltons. It has an isoelectric point of 7.0 +/- 0.1. It has an optimal activity between pH 5.0 and 7.0. It has no cofactor requirement and is not inhibited by EDTA. Uracil-DNA-glycosylase is highly specific for DNA containing dUMP residues, releasing uracil as product of the reaction. It is 2-fold more active on single-stranded DNA than on double-stranded DNA. If it releases uracil dimers from ultraviolet-irradiated PBS1 DNA, it is at the threshold of the detection. The apparent Km is 7 X 10(-8) M, and uracil acts as a noncompetitive inhibitor with a Ki of 3.2 X 10(-4) M. Cis-syn cyclogbutadiuracil also is a potent inhibitor, while some analogs, produced by x-irradiation of uracil and thymine, are weak inhibitors. Spermine, between 10 and 400 microM, increases the enzymatic activity by 50% and is not inhibitory at other concentrations. Spermidine activates the enzyme at concentrations of 40 to 120 microM, but becomes inhibitory at 200 and 400 microM. A new finding is that drugs which intercalate in DNA, such as ethidium bromide and ellipticine, cause a 2- to 2.5-fold activation of this enzyme activity. The concentrations giving maximal activation depend on the drug. The enzyme does not behave as a processive enzyme during uracil excision.

DNA↗
PubMed1981

[Radiation-induced degradation of thymidine in deaerated aqueous solution].

The steady-state gamma radiolysis of deaerated aqueous solutions of thymidine generated a complex mixture of pyrimidine and nucleoside derivatives. Twenty-two of these compounds have been isolated and unambiguously characterized by spectroscopic methods including proton nuclear magnetic resonance and mass spectrometry. The major 5,6-saturated products has been identified as the 5R and 5S diastereoisomers of 5,6-dihydrothymidine and their mono and dihydroxylated derivatives on the 5 and/or 6-carbons. The G values of these various compounds has been determined. The roles of the primary reactive species derived from the radiolysis of water have been studied by using specific radical scavengers i.e., ethanol, t-butanol and potassium nitrate.

Cobalt Radioisotopes↗
PubMed1980

Conformational studies of alpha- and beta-pyrimidine 2'-deoxyribonucleosides in the syn and anti conformation.

Proton magnetic resonance studies of a series of pyrimidine alpha- and beta-2'-deoxyribosides in 2H2O have been carried out at 250 MHz. The H-H coupling constants and chemical shifts are discussed in terms of the molecular conformation. Methyl substitution at the 6-position of the base leads to rotation from the anti to the syn conformation in both anomeric species. In both series, the 2'endo pucker is preferred when the base is anti. Rotation into the syn conformation leads to a shift towards the 3'endo pucker, the shift being larger in the alpha-series. In the alpha-series, a correlation between the ring pucker and the C(4')-C(5') conformer distribution is revealed. Changes in geminal coupling constant, J2'2", are noted in the alpha-series and related to the sugar pucker.

Deoxyribonucleosides↗
PubMed1980

The thyroid-stimulating hormone response to thyrotropin-releasing hormone in mania and bipolar depression.

The release of thyroid-stimulating hormone (TSH) from the pituitary after infusion of 500 microgram of thyrotropin-releasing hormone (TRH) was decreased (p < 0.01) in manic patients and increased (p < 0.01) in bipolar depressed patients compared to a control group of patients with personality disorders. These results suggest that the TRH test may be useful in the diagnosis of psychiatric disorders and in the prediction of response to pharmacotherapy. We discuss the role of central monoaminergic systems in changes in the TSH response to TRH.

Affective Disorders, Psychotic↗
PubMed1979

Proton magnetic resonance studies of 5,6-saturated thymidine derivatives produced by ionizing radiation. Conformational analysis of 6-hydroxylated diastereoisomers.

The conformational properties of ten 6-hydroxylated dihydrothymidine derivatives including the various diastereoisomers of 5,6-dihydroxy-5,6-dihydrothymidine, 6-hydroxy-5,6-dihydrothymidine and 5-bromo-6-hydroxy-5,6-dihydrothymidine have been studied by 250 MHz proton magnetic resonance in aqueous solutions. A close correlation has been established between the carbon-6 configuration and the osidic conformation. The increase in the amplitude of the puckering within the furanose ring compared to that of thymidine or 2'-deoxyuridine is more pronounced for the levorotatory (6S) nucleosides than for the dextrorotatory (6R) diastereoisomers. The importance of the 2' endo conformer population decreases in the following order: (-) greater than (+) greater than thymidine. The absence of destabilizing effects on the g+ rotameric population about the C(4')-C(5') bond denotes the lack of any interaction between the exocyclic hydroxymethyl group and the 6-hydroxyl function or the 2-keto group. The 5,6-saturated nucleosides adopt a preferential anti conformation. The comparison has been extended to syn nucleosides which show opposite trends in the sugar conformation and g+ distribution.

Magnetic Resonance Spectroscopy↗