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Biomedical subjects

J Cadet

Publications and source records attributed to J Cadet.

At least 145 records · Page 8Linked to original sources
PubMed1990

Molecular mechanics and dynamics of DNA-furocoumarin complexes: effect of the aromatization of the pyrone ring on the intercalation geometry.

Results of molecular mechanics and dynamics calculations on intercalation complexes of DNA with various furocoumarins (psoralen, angelicin, 7-methylpyrido[3,4-c]psoralen and 7-methylpyrido[4,3-c]psoralen) and their corresponding aromatized derivatives are presented. These calculations were undertaken with the aim to elucidate the roles of the pyrone and pyridine moieties in the interactions which tend to orient the furocoumarins and pyridopsoralens between DNA base pairs. It appears that the intercalation geometries are very similar for the furocoumarins and related aromatized compounds. Therefore the oxygen and nitrogen atoms of the pyrone and pyridine moieties are not important in the orientation of the drug within the oligonucleotide.

Base Composition↗
PubMed1990

Identification of the two cis-syn [2 + 2] cycloadducts resulting from the photoreaction of 3-carbethoxypsoralen with 2'-deoxycytidine and 2'-deoxyuridine.

Near-ultraviolet photolysis of 2'-deoxycytidine (dCyd) and 3-carbethoxypsoralen (3-CPs) in the dry state was found to generate two main stable photoadducts which were separated by thin-layer and high-performance liquid chromatography. Fast atom bombardment and plasma desorption mass spectrometry analyses suggested that the bound molecule to 3-CPs is dCyd. These two compounds were found to produce the corresponding 2'-deoxyuridine (dUrd) derivatives through a deamination process when left in aqueous solutions with a lifetime close to 24 h at 20 degrees C. The chemical structure of the deaminated photoadducts was confirmed by photochemical synthesis using dUrd as the substrate. UV and fluorescent measurements indicated that the furan moiety of 3-CPs is involved in the photobinding reaction. The cyclobutane type structure of the modified dUrd derivatives was established on the basis of its photoreversibility and detailed 1H NMR analysis. The cis-syn stereoconfiguration of the two photocycloadducts was inferred from coupling constant considerations and on the basis of the complete assignment of the cyclobutyl protons, requiring the synthesis of deuterated nucleosides at pyrimidine carbon C(6). Further confirmation of the diastereoisomeric relationship between the two cis-syn dUrd <54' 65'> 3-CPs was provided by circular dichroism measurements.

Deoxycytidine↗
PubMed1990

Formation of cyclobutane thymine dimers photosensitized by pyridopsoralens: a triplet-triplet energy transfer mechanism.

The 365 nm irradiation of thymine thin films in the presence of pyridopsoralens is shown to induce the formation of cyclobutane thymine dimers, in contrast to other compounds such as 8- and 5-methoxypsoralen. In order to elucidate the mechanism of such a photosensitized reaction, we have determined the energy of the lowest triplet state (T1) of these compounds, using phosphorescence spectroscopy and CNDO/S quantum chemistry calculations. The T1 energy values were found to be significantly higher for pyridopsoralens--up to 0.3 eV--than for 8- and 5-methoxypsoralen (approximately 2.8 eV), which are not able to photoinduce cyclobutane thymine dimers. The determination of the relative efficiency of cyclobutane thymine dimer formation was performed using chromatographic analysis. A good correlation was found between the energy of the T1 state of the psoralen derivatives and the related cyclobutane thymine dimer formation. Moreover, the photosensitized cyclobutane thymine dimer formation appeared to be temperature-dependent. Our results are consistent with a mechanism involving a triplet energy transfer from the pyridopsoralen to thymine.

Energy Transfer↗
PubMed1989

UV-induced pyrimidine hydrates in DNA are repaired by bacterial and mammalian DNA glycosylase activities.

Escherichia coli endonuclease III and mammalian repair enzymes cleave UV-irradiated DNA at AP sites formed by the removal of cytosine photoproducts by the DNA glycosylase activity of these enzymes. Poly(dG-[3H]dC) was UV irradiated and incubated with purified endonuclease III. 3H-Containing material was released in a fashion consistent with Michaelis-Menten kinetics. This 3H material was determined to be cytosine by chromatography in two independent systems and microderivatization. 3H-Containing material was not released from nonirradiated copolymer. When poly(dA-[3H]dU) was UV irradiated, endonuclease III released 3H-containing material that coeluted with uracil hydrate (6-hydroxy-5,6-dihydrouracil). Similar results are obtained by using extracts of HeLa cells. There results indicate that the modified cytosine residue recognized by endonuclease III and the mammalian enzyme is cytosine hydrate (6-hydroxy-5,6-dihydrocytosine). Once released from DNA through DNA-glycosylase action, the compound eliminates water, reverting to cytosine. This is consistent with the known instability of cytosine hydrate. The repairability of cytosine hydrate in DNA suggests that it is stable in DNA and potentially genotoxic.

Animals↗
PubMed1989

Plasma desorption mass spectrometric study of UV-induced lesions within DNA model compounds.

Positive and negative plasma desorption (PD) mass spectra of the di-deoxyribonucleoside monophosphate d(TpT) and of its biologically relevant ultraviolet-induced intramolecular photodimers are examined and discussed. The photodimers which were analysed by PD mass spectrometry include the cis-syn and trans-syn cyclobutyl isomers d(T[p]T), the pyrimidine-pyrimidone photoadduct (6-4)d(TpT) and its Dewar valence isomer. Molecular ions, quasi-molecular ions and several fragment ions are observed in all cases. It is shown that, despite the absence of mass differences between these dinucleoside monophosphates, the fragmentation pattern differs significantly between the two main classes: cyclobutane dimers and (6-4) adducts. PD mass spectrometry can therefore be envisaged for characterizing their formation within short DNA fragments.

DNA↗
PubMed1989

[Nonsurgical treatment: a long-term study].

This retrospective study was carried out on 20 patients with periodontal lesions treated by the same operator by scaling root planing. The investigation was designed to study the variability of the level of attachments through different charts of probing before and after treatment over a period of 5 years maintenance. Through efficient scaling and root planing different results were obtained according to sites of different localisations and depth. It shows the uncertain and occasional characteristics of periodontal lesions, and gives useful informations for treatment choices and regular maintenance program.

Dental Prophylaxis↗
PubMed1988

Nuclear magnetic resonance studies of cis-syn, trans-syn, and 6-4 photodimers of thymidylyl(3'-5')thymidine monophosphate and cis-syn photodimers of thymidylyl(3'-5')thymidine cyanoethyl phosphotriester.

Three out of four possible photodimers of thymidylyl(3'-5')thymidine monophosphates (i.e., cis-syn, 6-4, and one of the trans-syn) and two structural isomers (i.e., R and S forms) of cis-syn-thymidylyl(3'-5')thymidine cyanoethyl phosphotriester have been isolated and purified from the reaction mixtures after UV irradiation and studied by multinuclear magnetic resonance Spectroscopy. All five inter thymine base linked photodimers have grossly similar structures which are quite different from those of the parent thymidylyl(3'-5')thymidine. The base of Tp- is in the syn conformation, and that of -pT it is in the anti conformation. The sugar puckering of Tp- is dominated by the 2E conformer, but in -pT it is in 4E; except for the conformer around C5'-O5' bond, the 6-4 isomer is very similar to those of cis-syn and trans-syn conformation. As expected, there are sugar-phosphate backbone distortions in the phosphotriesters, due to the neutralization of the negative charge of the phosphate. In general the structures of all five photodimers are very close to those of the cis-syn photodimer of thymidylyl(3'-5')thymidine monophosphate cyanoethyl ester as studied by X-ray diffraction [Cadet, J., Voituriez, L., Hruska, F. E., & Grand, A. (1985) Biopolymers 24, 897-903; Hruska, F. E., Voituriez, L., Grand, A., & Cadet, J. (1986) Biopolymers 25, 1401-1417]. While the trans-syn photodimer has two structural isomers, only one [C6(of Tp-)-R] was produced by the UV irradiation and studied.

Dinucleoside Phosphates↗
PubMed1988

A new class of psoralen photoadducts to DNA components: isolation and characterization of 8-MOP adducts to the osidic moiety of 2'-deoxyadenosine.

The near-UV-induced photoreaction of the bifunctional 8-methoxypsoralen (8-MOP) with 2'-deoxyadenosine (dAdo) was investigated in the dry state. Four main monoadducts of 8-MOP to 2'-deoxyadenosine were separated by high performance liquid chromatography and subsequently characterized by soft ionization mass spectrometry (fast atom bombardment and plasma desorption mass spectrometries) and extensive 1H NMR analysis including nuclear Overhauser effect (NOE) measurements. These new types of furocoumarin-nucleic acid component which appear to be specific to 2'-deoxyadenosine were shown to result from recombination of the 3,4-dihydropyron-4-yl radical of 8-MOP with 2'-deoxyadenosyl radical either at the 1' or the 5' position.

Chromatography, High Pressure Liquid↗
PubMed1988

The repairability of oxidative free radical mediated damage to DNA: a review.

Many DNA repair enzyme activities are present in both prokaryotic and eukaryotic organisms. Among these are DNA exo- and endonucleases and DNA glycosylases which remove oxidatively damaged portions of the DNA molecule, thereby initiating excision-repair. The existence of these enzymes may be taken as evidence that cellular DNA is continuously subject to endogenous oxidative stress. Many of the lesions introduced by ionizing and ultraviolet radiation are identical to those introduced into DNA by reactive oxygen species generated by activated white cells, and are substrates for the repair enzymes. The chemical nature of the lesions, their biologic effects, and the mechanism of their repairability are described.

Animals↗
PubMed1988

Formation of cyclopyrimidines via the direct effects of gamma radiation of pyrimidine nucleosides.

Continuing our study of the direct effects of gamma radiation on DNA and its model compounds, we have isolated and characterized quantitatively an important lesion formed by irradiating pyrimidine 2'-deoxyribonucleosides in frozen aqueous solution. We report here the formation of 5',6-cyclo-5,6-dihydropyrimidine nucleosides via hydrogen abstraction at C5' of the osidic moiety with subsequent intramolecular attack at C6 of the base. We have so far managed to isolate six of the possible eight diastereomers of 5',6-cyclo-5,6-dihydrothymidine, and all four possible 5',6-cyclo-5,6-dihydro-2'-deoxyuridines formed by irradiation of 2'-deoxycytidine. Also presented is a detailed discussion of the configurational analysis of each isomer based on 1H NMR data.

Freezing↗
PubMed1987

Specific deprotonation reactions of the pyrimidine radical cation resulting from the menadione mediated photosensitization of 2'-deoxycytidine.

Menadione(2-methyl-1,4-naphthoquinone) was shown to sensitize 2'-deoxycytidine to near ultraviolet light according to two main mechanisms. Reaction of a water molecule with the initially photo-induced pyrimidine radical cation and subsequent addition of molecular oxygen leads to the preponderant formation of the four cis and trans diastereoisomers of 5,6-dihydroxy-5,6-dihydro-2'-deoxyuridine. Pyrimidine ring opening and rearrangement products are also generated through the intermediate 6-hydroxy-5,6-dihydro-2'-deoxyurid-5-yl radical. The competitive deprotonation reaction of the radical cation is likely to involve two sites. Loss of an amino group proton is the likely initial event to explain the formation of 2'-deoxyuridine which is resistant to further photooxidation. The second deprotonation reaction involves the osidic carbon C(1'). The resulting radical will further react with oxygen leading to the release of free cytosine with concomitant formation of 2-deoxy-D-ribono-1,4-lactone. This reaction which is not prevented by hydroxyl radical scavengers constitutes to our knowledge the first example of a pyrimidine radical which is able to initiate selective intramolecular reaction at position 1 within the sugar moiety.

Carbon Radioisotopes↗
PubMed1987

Quantitative measurement of the diastereoisomers of cis thymidine glycol in gamma-irradiated DNA.

A technique for determining the relative content of each of the diastereoisomers of cis thymidine glycol (dTG) in DNA exposed to ionizing radiation has been developed. [3H]thymidine DNA was gamma-irradiated, digested to 2'-deoxyribonucleosides, authentic [14C] (+, -) cis dTG added to the digestate and the mixture resolved by HPLC. 3H fractions coeluting with [14C] (+, -) dTG were collected and acetylated. The acetoxy derivatives of (+) and (-) cis dTG were easily resolved by a second HPLC analysis and their absolute configuration determined by NMR and mass spectroscopies. We have constructed a dose-response curve for formation of each isomer in gamma-irradiated DNA and shown that they are formed in equal amounts. This technique may be used to determine the relative formation of cis dTG isomers in DNA resulting from other oxidative stresses and whether repair of these is influenced by their configuration.

Acetylation↗
PubMed1987

[Tissue reactions induced by provoked tooth displacement in experimental periodontal lysis].

A dental appliance with a spring used to induce a mesial movement of the lower molars was placed in the mouth of two groups of golden hamsters, one control and the other submitted to the hyperglucidic diet of Keyes and Jordan. The analysis and histological comparison of the tissue reactions showed important differences in both groups. The alveolar wall remodeling in the experimental group was inhibited as well as the resorption of the hyaline zones.

Alveolar Process↗