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E Ben-Hur

Publications and source records attributed to E Ben-Hur.

At least 73 records · Page 4Linked to original sources
PubMed1988

Release of clotting factors from photosensitized endothelial cells: a possible trigger for blood vessel occlusion by photodynamic therapy.

Photodynamic treatment of solid tumors results in the occlusion of blood vessels in the treated tissue. We hypothesize that this process is triggered by the release of one or more clotting factors from the photodamaged endothelial cells. Experimental evidence is presented that immediately after photodynamic treatment, cultured endothelial cells start releasing clotting factors into the medium in a dose range of minimal cytotoxicity.

Adrenal Medulla↗
PubMed1988

Recovery of Chinese hamster cells following photosensitization by zinc tetrahydroxyphthalocyanine.

The phthalocyanine dyes are attractive sensitizers for photodynamic therapy of cancer. The light fluence response curves for photocytotoxicity of zinc tetrahydroxyphthalocyanine were constructed using the colony-forming ability of Chinese hamster cells as an end-point. The survival curve of cells photosensitized to white light by this dye has a pronounced shoulder followed by an exponential decline. Postillumination hypertonic treatment (0.5 M NaCl for 20 min at 37 degrees C) enhanced log-phase killing, although to a lesser extent than after exposure to ionizing radiation. While such an enhancement usually indicates that the cells are able to repair potentially lethal damage, delayed trypsinization of photosensitized cells in plateau-phase failed to show a significant increase in cell survival. Thus, the repair of such a damage in plateau-phase is apparently absent. Experiments with split light fluence indicated that log-phase cells can repair sublethal damage during a 24 h interval, as evidenced by the reappearance of the shoulder on the split-dose survival curve.

Animals↗
PubMed1988

Combined action of phthalocyanine photosensitization and gamma-radiation on mammalian cells.

The response of Chinese hamster cells and human lymphocytes to the combined action of photosensitization by chloroaluminium phthalocyanine tetrasulfonate and gamma-radiation was studied using colony-forming ability and [3H]thymidine incorporation following mitogenic stimulation respectively, as endpoints. The action of both treatments was usually additive regardless of the sequence of application. However, in human lymphocytes irradiated at low temperature, the photosensitization interacted synergistically with the subsequent ionizing radiation; in this experiment the initial photosensitization reduced the yield of micronuclei produced by gamma-radiation.

Animals↗
PubMed1987

Mechanism of uptake of sulfonated metallophthalocyanines by cultured mammalian cells.

The uptake of several metallophthalocyanine tetrasulfonates by cultured Chinese hamster cells was studied. Uranyl- and chloraluminium were taken up at the highest rate followed by Ni-, Zn-, Cu-, Co- and dichlorosilicon-phthalocyanine tetrasulfonate. The uptake from the growth medium containing 10% serum in which only 15% of the dye is not bound to serum proteins was 5--18-fold slower than in the absence of serum, suggesting that most of the uptake is of free dye. Using gel filtration to separate tightly protein-bound dye from the free dye, binding curves were constructed that varied in slope and saturation values for the different compounds. At saturation, the number of dye molecules bound per serum albumin molecule varied from 1 for vanadyl- and cobalt-, to 4 for uranyl-phthalocyanine tetrsulfonate. Absorption spectra of the various phthalocyanines indicated that under physiological conditions, all dyes, with the exception of chloroaluminum- and dichlorosilicon-phthalocyanine tetrasulfonate, were aggregated. The rate of uptake was unrelated to the state of aggregation. The rate of uptake was temperature dependent at intervals longer than 1 h. At shorter times, very little temperature dependence was observed. These results suggest that the uptake process takes place in two steps. The first step is passive, involving binding of metallophthalocyanine tetrasulfonate to a receptor on the cell membrane, while the second one is active and involves internalization of the bound dye.

Animals↗
PubMed1987

Effect of light fluence rate on mammalian cells photosensitization by chloroaluminium phthalocyanine tetrasulphonate.

Phthalocyanines are photosensitizers evaluated for use in photodynamic therapy of cancer. As such, the dependence of the bioresponse on the light fluence rate may be of clinical importance. The effect of the fluence rate of white light from 0.165 to 3.3 kJ m-2 min-1 was studied in Chinese hamster cells and human lymphocytes, using as endpoints colony-forming ability and inhibition of [3H]thymidine incorporation following mitogenic stimulation and dye-photoactivation, respectively. Using Chinese hamster cells exposed to photoexcited chloroaluminium phthalocyanine tetrasulphonate in PBS solution, cytotoxicity was diminished as the fluence rate was reduced. In human lymphocytes changing the fluence rate between 0.33 and 3.3 kJ m-2 min-1 affected the response in a way similar to that of Chinese hamster cells. Human lymphocytes, when exposed to incremental increasing light fluences, 4 h after a conditioning dose, were able to recover from phthalocyanine-induced photodamage, as evidenced by the reappearance of a shoulder on the dose-effect curve. This recovery process during a protracted light exposure, could explain the reduced sensitivity to phthalocyanine photosensitization, compared to exposure at high fluence rates.

Animals↗
PubMed1987

Are single or multiple mechanisms involved in radiation-induced mammalian cell killing?

The survival curve of repair-competent mammalian cells exposed to X- or to gamma-rays has a shoulder usually followed by a region of exponential survival. A curve of this shape results from the accumulation of subeffective damage in the shoulder region. This damage has been called sublethal [Elkind & Sutton (1959), Nature, 184, 1293], a designation the basis for which has been questioned by Alper [(1977), Brit. J. Radiol., 50, 459] who noted that if the shoulder results from the progressive reduction of a repair capacity, then the damage would be potentially lethal. A series of experiments is analyzed to show that requiring an equivalence between sublethal and potentially lethal damage has limited usefulness because as many questions are raised as are answered. Moreover, the sector of repair corresponding to the shoulder region is small compared to the sector of damage which must be repaired if only a minority of the lesions in DNA are effective. It is concluded that multiple mechanism may be involved in cell killing and, in addition, that the processes connected with the shoulder region of the survival curve amount to only the tip of an iceberg whose size and properties are yet to be fully appreciated.

Animals↗
PubMed1986

Photohemolysis of human erythrocytes induced by aluminum phthalocyanine tetrasulfonate.

The phthalocyanines are a new class of photosensitizers with promising properties for use in photodynamic therapy of cancer [E. Ben-Hur and I. Rosenthal (1985) Int. J. Radiat. Biol., 47, 145--147]. The ability of aluminum phthalocyanine tetrasulfonate (AlPCS) to cause membrane damage upon light exposure was tested using photohemolysis of human erythrocytes as an endpoint. AlPCS was found to be quite efficient in causing red blood cell lysis. Photohemolysis dependency on the light fluence had a characteristic sigmoidal shape. The light fluence required for 50% hemolysis was inversely proportional to AlPCS concentration. Neither singlet oxygen nor hydroxyl radicals appear to be involved in the photohemolysis induced by AlPCS. This is inferred from the observation that exposure of erythrocytes in the presence of D2O or glycerol did not affect the light fluence response curve. These data suggest that photosensitization by AlPCS can cause membrane damage and that this damage may be responsible for cell killing.

Erythrocyte Membrane↗
PubMed1986

Photodynamic treatment of transplantable bladder tumors in rodents after pretreatment with chloroaluminum tetrasulfophthalocyanine.

Chloroaluminum tetrasulfophthalocyanine (AlPCS) was used as a photosensitizer for the photodynamic treatment of transplantable N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) induced urothelial tumors. Two groups of six rats each were injected with AlPCS (three micrograms./gm. body weight) and 24 hours after injection underwent photodynamic treatment with red light (greater than 590 nm., 360 joules/cm.2). Tumors examined four hours (Group I) and 24 hours (Group II) after the completion of phototreatment showed extensive hemorrhagic necrosis. Tumors treated with AlPCS alone showed no changes. In two other groups of six rats each, blood flow to tumors treated with AlPCS alone (Group III) and AlPCS plus light (Group IV) was measured using the radioactive microsphere technique. AlPCS plus light resulted in a significant decrease (p less than .05) in tumor blood flow within 10 minutes of completion of phototreatment while AlPCS alone had no effect on tumor blood flow. These findings are similar to those observed when higher doses (10 micrograms./gm. to 20 micrograms./gm. body weight) of hematophorphyrin derivative (HpD) and light were used for phototreatment of FANFT induced tumors. AlPCS is a stable sulfonated derivative of tetraazotetrabenzoporphyrin which absorbs maximally in the red portion of the visible spectrum, a region with good tissue penetration properties. These studies suggest the AlPCS may be a useful new agent for photodynamic therapy of cancer.

Animals↗
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

Poly(ADP-ribose) and the recovery from damage in Chinese hamster cells due to 5-bromodeoxyuridine photolysis.

Exposure of Chinese hamster cells to near-u.v. light, following the uniform incorporation of 5-bromodeoxyuridine (BrdUrd) into their DNA, resulted in cell killing that was close to exponential. An inhibitor of poly(ADP-ribose) synthesis, 3-aminobenzamide (3-ABA), enhanced the cytotoxic effect of this treatment when present for 2 h at 20 mM after light exposure. The dose modifying factor was 1.4. Under conditions that resulted in a sigmoidal survival curve (a 30 min BrdUrd pulse in S phase, followed 90 min later by light exposure) the effect of 3-ABA was to remove the shoulder of the survival curve with very little change in its final slope. Using various inhibitors of ADP-ribosyl transferase (ADPRT) the enhanced cell killing was found to correlate with the inhibitors' relative potency. Cellular NAD+, the substrate for poly(ADP-ribose) synthesis, was rapidly depleted after exposure. This depletion was largely prevented by 3-ABA; the activity of ADPRT increased with the fluence of near-u.v. light; and the concentration of cellular NAD+ decreased with exposure. ADPRT activity was maximal immediately after exposure to near u.v. light and then decayed to pre-exposure levels within 30 min (37 degrees C). The enhanced cytotoxicity of BrdUrd + near-u.v. light, when followed by 3-ABA treatment, disappeared at a rate similar to that of the decay in ADPRT activity. We conclude from these results that poly(ADP-ribose) synthesis is important for the recovery from BrdUrd photolysis damage in DNA. Because this damage and its repair are relatively specific (e.g. compared to ionizing radiation) and relatively easy to manipulate, it could serve as a model system for the study of the role of poly(ADP-ribose) in the repair of DNA damage.

Animals↗
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↗