Deregulation of cell proliferation by polycyclic aromatic hydrocarbons in human breast carcinoma MCF-7 cells reflects both genotoxic and nongenotoxic events.

Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), are carcinogens suggested to be involved in development of human cancer. Several recent studies have reported that PAHs can activate estrogen receptors (ER), either directly or indirectly by producing estrogenic metabolites. We hypothesized that the activation of ER by PAHs or their metabolites could induce cell proliferation in estrogen-sensitive cells. In the present study, we found that two PAHs, benz[a]anthracene (BaA) and BaP, can stimulate proliferation of human breast carcinoma MCF-7 cells at concentrations 100 nM and higher. This effect was ER-dependent, because it was blocked by the pure antiestrogen ICI 182,780. Although both PAHs partially inhibited S-phase entry and DNA synthesis induced by 17beta-estradiol, they stimulated S-phase entry when applied to MCF-7 cells synchronized by serum deprivation. This was in contrast with model antiestrogenic aryl hydrocarbon receptor ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin, which fully suppressed S-phase entry. BaP, which is a strong mutagen, was found to induce p53 tumor suppressor expression, a partial S-phase arrest and at higher concentrations also cell death. Pifithrin-alpha, a synthetic inhibitor of p53 activity, abolished both S-phase arrest and apoptosis induced by genotoxic PAHs, and it potentiated the proliferative effect of BaP. Thus, both genotoxic and nongenotoxic events seem to interact in the effects of BaP on cell proliferation. Taken together, our data indicate that both BaA and BaP can stimulate cell proliferation through activation of ER. The proliferative effects of these carcinogenic compounds might contribute to tumor promotion in estrogen-sensitive tissues.     

The cellular uptake of sensitizers bound to cyclodextrin carriers

Photodynamic therapy of cancer uses the interaction of sensitizers and light to destroy cancer cells. In this study we tested the cellular uptake of meso-tetrakis(4-sulfonatophenyl)porphine (TPPS4) and its complex PdTPPS4 in the presence or absence of 2-hydroxypropyl-cyclodextrins (hpCDs) on G361 human melanoma cells. Self-fluorescence in G361 cells were measured by Perkin-Elmer LS50B luminometer equipped with well plate reader accessory. Morphological changes in cells have been evaluated using inversion fluorescent microscope Olympus IX 70 and image analysis. The uptake of the sensitizer PdTPPS4 at the given time interval from 1 to 48 hours is markedly higher than the uptake of TPPS4. The highest uptake was found for sensitizer PdTPPS4 in combination with hpbetaCD. TPPS4 and PdTPPS4 especially in the supramolecular complex with nontoxic cyclodextrin carriers represent efficient sensitizers for photodynamic therapy in vitro on G361 cells.     

Malignant fibrous histiocytoma arising in a recurrent chordoma

Summary We present the case of a sacrococcygeal chordoma which recurred 15 years after the radical removal as a soft tissue tumor in the gluteal musculature. This tumor consisted of two parts: a chordoma without symptoms of aggressive cellular proliferation and a malignant fibrous histiocytoma. During the following 4 years several local recurrences of the malignant fibrous histiocytoma occurred in the gluteal musculature. The patient finally died of lung metastases. No chordoma tumor tissue was found in the lungs, in the gluteal musculature or in the sacrococcygeal bone area. Histology including electron microscopy revealed no proof of a transition of chordoma into malignant fibrous histiocytoma. It must be assumed that the secondary soft tissue tumor originated from residual chordoma cells which were implanted during the operation of the primary tumor. It remains unclear whether the malignant fibrous histiocytoma arose from mesenchymal stromal cells within the chordoma or directly from primitive neuroectodermal chorda cells which possess the ability to differentiate into a variety of cell types including mesenchymal cells.     

Über die Wechselwirkung des Katalysators und Cokatalysators mit dem Monomeren und dem Polymeren bei der kationischen Polymerisation des Isobutylens. II. Modellstudium des Polymerisations-Depolymerisations-Gleichgewichts im System Triisobutylen/AlBr3/DBr/Heptan

In the reaction of triisobutylene with AlBr₃/DBr system, backbone isomerization and formation of higher oligomers takes place, in addition to deuteration. Both reactions are explained by the cleavage of the backbone bonds of the intermediate carbonium ions. The fragments formed can react with other components of the reaction system. The possible role of these reactions in the mechanism of termination and chain transfer in the cationic polymerization of isobutylene is discussed briefly.     

Partial purification and characterization of anhydrotetracycline oxygenase of Streptomyces aureofaciens

Anhydrotetracycline oxygenase was purified both by affinity chromatography and by hydrophobic interaction chromatography. Molecular weight of anhydrotetracycline oxygenase was determined to be 115,000 by Sephadex G-200 gel filtration. Using preparative isoelectric focusing the isoelectric point of the enzyme was estimated to be 5.3. The enzyme showed a sensitivity to thiol-specific inhibitors. During the hydrophobic interaction purification step, the activity dropped considerably. Reactivation occurred when a heat treated crude extract was added to the reaction mixture.     

Properties of visual evoked potentials to onset of movement on a television screen

In 80 subjects the dependence of movement-onset visual evoked potentials on some measures of stimulation was examined, and these responses were compared with pattern-reversal visual evoked potentials to verify the effectiveness of pattern movement application for visual evoked potential acquisition. Horizontally moving vertical gratings were generated on a television screen. The typical movement-onset reactions were characterized by one marked negative peak only, with a peak time between 140 and 200ms. In all subjects the sufficient stimulus duration for acquisition of movement-onset-related visual evoked potentials was 100ms; in some cases it was only 20ms. Higher velocity (5.6°/s) produced higher amplitudes of movement-onset visual evoked potentials than did the lower velocity (2.8°/s). In 80% of subjects, the more distinct reactions were found in the leads from lateral occipital areas (in 60% from the right hemisphere), with no correlation to handedness of subjects. Unlike pattern-reversal visual evoked potentials, the movement-onset responses tended to be larger to extramacular stimulation (annular target of 5°–9°) than to macular stimulation (circular target of 5° diameter).Abbreviation PREP pattern-reversal visual evoked potentials     

Flexible tantalum stents: Effects in the stenotic canine urethra

Purpose Evaluate the effects of flexible tantalum stents (Strecker) implanted into stenotic canine urethras.Methods Eight conditioned, adult, German shepherd dogs, weighing 30–40 kg, were used. Strictures were created surgically in the bulbar urethra just proximal to the os penis. Two months postsurgery, strictures were documented radiographically and then balloon dilated. Following dilatation, a single Strecker stent was placed across the stricture. Stents were 7 mm in expanded diameter and either 2 or 4 cm in length. Retrograde urethrography was performed immediately after stent placement and then biweekly for up to 12 months. Two dogs were sacrificed at 2, 4, 6, and 12 months post-stenting, and necropsy was performed. The urethra was excised, fixed, and examined by scanning electron and light microscopy.Results Clinical success was achieved without complications in all animals. Hyperplasia of the urothelium was noted 4–6 weeks after stent placement and was most pronounced at 4–6 months. Mucosal folds were found between the stent struts. Restenosis occurred at the distal end of the stent in one dog. Histological alterations were noted in the deeper layers of the urethral wall.Conclusion Strecker stents were well tolerated in all animals and seem useful for the treatment of urethral strictures.Presented at CIRSE Annual Meeting and Postgraduate Course, Budapest, June 20–24, 1993