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Biomedical subjects

I Rosenthal

Publications and source records attributed to I Rosenthal.

At least 55 records · Page 3Linked to original sources
PubMed1986

The role of molecular oxygen in the photodynamic effect of phthalocyanines.

Phthalocyanines are a class of mammalian cell photosensitizers which may be useful in photodynamic therapy for cancer. Chloroaluminum phthalocyanine tetrasulfonate was incubated with Chinese hamster cells in culture and exposed to white light at different concentrations of oxygen. The ability of the cells to form colonies served as an end point for the photobiological effect of the dye. The efficiency of photoinactivation of the sensitized cells decreased with decreasing oxygen concentration. Very little photoinactivation was observed when the atmosphere equilibrated with the cells was oxygen-free nitrogen. At an oxygen partial pressure of 2.5 mm Hg, photoinactivation was reduced by 50% compared to ambient atmosphere. In an attempt to understand the nature of the interaction between excited dyes and oxygen, the ability of several phthalocyanines to photogenerate singlet oxygen was measured. Thus phthalocyanines containing paramagnetic ions (copper, iron, vanadyl) do not generate 1O2 in contradistinction to diamagnetic metals (zinc and aluminum). The latter are efficient photosensitizers, while the former have little if any photobiological activity. In spite of this correlation, singlet oxygen may not be the intermediate involved in cytotoxicity. The reasons are discussed.

Animals↗
PubMed1985

Histamine reduces the deamination of putrescine in vitro--but also in vivo?

The diamine oxidase catalysed deamination of putrescine was reduced in vitro by histamine at concentrations occurring in the gut. An oral application of histamine, however, had no effect on the enzymic activity. When the histamine was injected i.p. a decrease of intestinal diamine oxidase activity was observed which, however, did not depend on histamine but probably on an unspecific irritation of the gut.

Amine Oxidase (Copper-Containing)↗
PubMed1985

Photochemical generation of superoxide radical and the cytotoxicity of phthalocyanines.

The effect of the central metal atom on the photodynamic activity of phthalocyanine dyes has been estimated by cytotoxicity to cultured Chinese hamster cells. Chloroaluminium phthalocyanine,, followed by the Zn- derivate, were found to be the only active dyes. In parallel it was found that visible light (615 +/- 10 nm) excitation of phthalocyanines dissolved in dimethylsulphoxide in the presence of oxygen generates superoxide radical anion. O2- radicals were spin--trapped with 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) and identified by electron spin resonance. The quantum yields for O2- generation range from 10(-5) (Zn-phthalocyanine) to 4.2 X 10(-4) (Ga-phthalocyanine). The efficiency of generating O2- was apparently uncorrelated with the phototoxicity of the same dyes. Furthermore, the biological photodamage could not be inhibited by the addition of superoxide dismutase. It is concluded that O2- is involved very little, if at all, in the phthalocyanine-induced photo-killing of mammalian cells.

Animals↗
PubMed1985

Effect of free-radical and oxygen scavengers on photochemically generated oxygen toxicity and on the aerotolerance of Campylobacter jejuni.

Exposure of a nutrient agar medium to the combined action of fluorescent light and air produced toxic factors in the medium which affected the growth of Campylobacter jejuni. Sodium dithionite (5-10 mM), a powerful reducing agent, and catalase were effective in counteracting the injurious action of light and air. Among the quenchers of singlet oxygen tested, only histidine had a beneficial effect on the recovery of C. jejuni in the photo-oxidized medium, while the addition of superoxide dismutase, a hydroxyl radical scavenger such as cysteamine, or the free radical antioxidants tocopherol and butylated hydroxy toluene, did not increase the recovery rate of photochemically injured cells. Histidine (40 mM) and dithionite (5-10 mM) also assisted recovery of C. jejuni inoculated on nutrient agar stored in air in the dark. Cysteamine and dithionite were toxic to Campylobacter when added at concentrations of greater than or equal to 10 mM and greater than or equal to 20 mM, respectively. A high inoculum of C. jejuni could not be recovered in unsupplemented nutrient agar incubated in air but was recovered in atmospheres containing 17 or 21% oxygen plus 10% carbon dioxide. The addition of dithionite, catalase or histidine resulted some colony formation on nutrient agar incubated in air. Among the scavengers tested, only dithionite was consistently able to maintain the viability of C. jejuni on nutrient agar stored in air for longer than 4 weeks. In view of the ability of catalase, dithionite and histidine to enhance the aerotolerance of C. jejuni, it is concluded that various oxygen species might be involved in the toxicity of high levels of oxygen.

Aerobiosis↗
PubMed1985

Factors affecting the photokilling of cultured Chinese hamster cells by phthalocyanines.

Chloroaluminum phthalocyanine (CAPC) was recently shown to sensitize the inactivation of cultured Chinese hamster cells by visible light. Several factors affecting the photodynamic action of CAPC have been defined in the present study. Thus the photosensitized inactivation of Chinese hamster cells is not affected by superoxide dismutase, suggesting that O-2 radicals are not involved in the process. Postillumination treatments with D2O or heat (42 degrees C, 90 min) enhanced CAPC-induced photosensitivity, indicating the existence of a repair mechanism for photodamage. Preillumination treatments with sodium salicylate and 5-bromodeoxyuridine also enhanced photosensitivity. The later observation suggests that CAPC-induced DNA damage is potentially lethal. However, 3-aminobenzamide, a potent inhibitor of poly(ADP-ribose) synthesis which is involved in repair of DNA strand breakage, had no effect on the photosensitivity. Photosensitized inactivation by CAPC is dependent on the pH value of the medium during irradiation. Thus, in the range of pH values 6-8, the sensitivity was increased at the lower values.

Animals↗
PubMed1983

Pulse radiolysis studies of some aza analogues of nucleic acid components.

The technique of pulse radiolysis has been utilized to study the reactions of some aza analogues of nucleic acid components with hydrated electrons and OH radicals. The absorption spectra of the transient free radical adducts which result from these reactions and their decay kinetics were determined. The 5-aza analogues gave similar results to those of pyrimidine bases. The 6-aza analogues also showed similar kinetics, however, transient spectra were different. The presence of the sugar moiety in these aza analogues changed the rate law of the OH adduct transient decay from second order to first order kinetics. This finding may have implications for the understanding of the radiation chemistry of DNA.

Aza Compounds↗
PubMed1981

Photochemistry of pyrimidine bases as studied by e.s.r. and spin-trapping.

The direct photoexcitation of pyrimidine bases in D2O solutions yields free radicals which could be conveniently identified by spin-trapping with 2-methyl-2-nitrosopropane. Most of the radicals formed were attributed to D-addition to one end of the 5,6 double bond. However, orotic acid and iso-orotic acid yielded N(3) centred free radicals, formed by homolytic cleavage of the N-H bond. No indication could be found for a free radical involvement in the photocleavage of cyclobutane-type pyrimidine dimers.

Electron Spin Resonance Spectroscopy↗
PubMed1981

Hydrogen-deuterium exchange in gamma-irradiated polycrystalline DL-alanine: a spin-trapping and e.s.r. study.

The hydrogen-deuterium exchange reactions in gamma-irradiated DL-alanine in the solid state were investigated by spin-trapping and electron spin resonance (e.s.r) using selectively deuterated DL-alanine. Subsequent to gamma-radiolysis at 30 degrees C, polycrystalline DL-alanine was dissolved in aqueous solutions of 2-methyl-2-nitrosopropane and the extent of H-D exchange of the deamination radicals was followed by e.s.r. After formation of the deamination radicals, four exchange reactions were found to occur between the radicals and the surrounding undamaged molecules. The first reaction, which occurs between the hydrogens of the C-2 carbon of the radicals and those of the methyl groups of the neighbouring molecules, can be followed at room temperature. The three other reactions could be conveniently monitored in gamma-irradiated polycrystalline alanine at 110 degrees C. The first of the other three reactions takes place between the methyl hydrogens of the radicals and the C-2 hydrogens of nearby molecules, while the remaining processes involve exchange between the hydrogen atoms of the amino group and those on the C-2 and C-3 carbon atoms of the deamination radical.

Alanine↗
PubMed1981

E.s.r. and spin-trapping studies of dihydropyrimidines. gamma-Radiolysis in the polycrystalline state and U.V. photolysis in aqueous solution.

gamma-Radiolysis in the polycrystalline state and U.V. photolysis in aqueous solution at 220 nm of several dihydropyrimidines and their derivatives have been investigated by spin-trapping and electron spin resonance. 2-Methyl-2-nitrosopropane was used as the spin-trap. The spin-adducts of the 6-yl radicals obtained fall into two categories. Those from dihydro-1-methyluracil, dihydro-6-methyluracil, dihydro-1-ethyluracil and dihydro-1-methylcytosine exhibit a beta-nitrogen hyperfine coupling constant (alpha beta N) equal to or less than 2.0 G while the ones fom dihydro-orotic acid, dihydrouracil and dihydrothymine showed much larger alpha beta N values (greater than 3.3 G). Dihydrouridine gives radicals characteristic of both the dihydropyrimidine ring and the sugar moiety. The same radicals were obtained by gamma-radiolysis or U.V. photolysis. For all the 5-yl radicals obtained by U.V. photolysis, a direct photoexcitation mechanism is proposed.

Crystallization↗
PubMed1980

pH dependence of the phototoxic and photomutagenic effects of chlorpromazine.

The pH dependence of the phototoxic effects of chloropromazine (CPZ) in Escherichia coli, Salmonella typhimurium and Chinese hamster cells were studied at pH 6--8. All three biological systems displayed higher photosensitization of the drug at lower pH-values. In S. typhimurium the combined action of drug and light also showed mutagenic activity which correlated with toxicity when exposed at pH 7 or 8. When solutions of protein or DNA and CPZ were exposed to near ultraviolet (UV) light, the drug became covalently attached to the macromolecules. This binding was pH dependent but did not correlate with the effects in vivo. It was found however that the permeability of the cells to the drug was enhanced at lower pH-values. It is suggested that the enhanced entrance of CPZ at lower pH-values into the cells facilitated the drug binding to DNA, RNA and proteins within the cells upon light exposure, and that this is the basis for the enhanced phototoxicity and mutagenicity of CPZ.

Animals↗
PubMed1980

Application of mutagenicity test for milk.

Mutagenic activity in milk and milk products was tested by the Salmonella mammalian-microsome mutagenicity test (Ames test). Salmonella mutants susceptible to base-pair substitution and frame-shift mutagens gave positive results with heat-sterilized milk, particularly after activation by the S-9 fraction of microsomes. Maximum increase of His+ revertants was more than twice the spontaneous increase. The chemical specification of the mutagenic activity was not yet defined, but it was present in the chloroform extract of milk.

Animals↗