Quercetin Prevents UV-lnduced Local Immunosuppression, but Does Not Affect UV-lnduced Tumor Growth in SKH-1 Hairless Mice

Abstract— Ultraviolet is thought to induce skin tumors by its dual activity as a mutagenic agent and a suppressor of cell-mediated immunity. In the present study the effects of quercetin, a flavonoid-containing compound, on carcinogenesis and immunosuppression were studied in SKH hairless mice exposed to suberythemal doses of UV for up to 17 weeks. It was found that quercetin did not affect the onset or growth of non-melanoma skin tumors resulting from UV exposure. In contrast, it prevented the suppression in contact hypersensitivity (CHS) to picryl chloride induced by UV. The mechanism of this prevention might be explained by the observation that the decreased number of epidermal Langerhans'cells is partly prevented by the quercetin. Quercetin did not alter the effects of UV in increasing numbers of spleen and lymph node cells, only partly in decreasing the CD8-positive cells in spleen cell populations and decreasing the lym-phoproliferative response of spleen cells to the mitogens concanavalin A and phytohemagglutinin. Thus oral quercetin did not prevent UV-induced carcinogenesis although it restored the skin-associated CHS response probably by protecting the antigen-presenting cells in the skin.     

Kinetics of disassembly of a DNA-bound porphyrin supramolecular array

trans-Bis(N-methylpyridinium-4-yl)diphenylporphine forms extended, organized assemblies on DNA templates under appropriate conditions of concentration, ionic strength, and temperature. Addition of beta-cyclodextrin to these arrays leads to their disassembly as evidenced by changes in extinction, circular dichroism, and resonance light scattering spectra. The structure or flexibility of the polymer template has an effect on the rate of disassembly; the reaction is faster on a poly(dG-dC)(2) surface than on ct DNA. The kinetic profiles for the disassembly process can be fit with great precision with a two-kinetic parameter equation in which the rate constant is itself a function of time. The reaction rate, studied in the presence of excess beta-CD, shows a dependence on the mode of detection. A model is presented to account for these observations in which the arrays become increasingly reactive with time due to beta-CD attack at the interior of the porphyrin assemblies as well as the ends.     

Magnetic resonance studies of laryngeal tumors implanted in nude mice: effect of treatment with bleomycin and electroporation

Recently, a new type of cancer treatment has been introduced that combines pulsed electric fields (PEF) with anticancer drugs. The proposed mode of action is that PEF create transient pores in the membranes which allow entry of drugs into the cells. This method increases cytotoxicity of some anticancer drugs like bleomycin (BLM) by 2-3 orders of magnitude, which, in turn, reduces systemic drug dosage without decreasing efficacy. In the present study, magnetic resonance imaging (MRI) was used to determine changes in apparent water self-diffusion coefficients (ADC) and spin-lattice (T(1)) and spin-spin (T(2)) relaxation times that occur in an animal laryngeal tumor (HEp-2 cells) model with BLM delivered by PEF. A Bruker 14 Tesla (600 MHz) wide-bore spectrometer with micro-imaging capability was used to generate all the data. Mice carrying approximately 8 mm tumors were treated with several combinations of drug and PEF. All measurements were made on tumor samples excised from mice 24 and 48 hours after treatment with (i) saline, intratumor injection (i.t.), (ii) BLM, i.t., (iii) saline with PEF, and (iv) BLM, i.t., followed by PEF. Although T(1) does not differ between the controls (i, ii, and iii) and full treatment (iv) 6.72 +/- 0.20 s vs. 6.31 +/- 1.7 s, T(2) for (iv) at 24 hours is significantly different from the controls 52.4 +/- 0.91 ms vs. 46.5 +/- 1.54 ms. T(2) differences between treatment and controls disappear at 48 hours. ADC increases significantly from 24 to 48 hours (7.31 +/- 0.16 x 10(-6) to 8.28 +/- 0.28 x 10(-6) cm(2)/sec, p = 0.05). Longer T(2) values may reflect early apoptosis and tumor death when the tumor is structurally less dense. Higher ADC's, associated with the periphery of the tumors and the central region, may indicate loose structural organization and necrosis resulting from the combination treatment.     

Synthesis and biological evaluation of the geometric farnesylated analogues of the a-factor mating peptide of Saccharomyces cerevisiae

The a-factor of Saccharomyces cerevisiae is a dodecapeptide pheromone (YIIKGVFWDPAC(Farnesyl)-OCH(3), 1), in which post-translational modification with a farnesyl isoprenoid and carboxymethyl group is required for full biological activity. This peptide has been used as a model system to explore the biological function of the farnesylcysteine moiety, which is found on and required for the biological activity of many key mammalian proteins. The objective of this particular study was the determination of the biological effect of double bond isomerization of the natural E, E-farnesyl moiety on the biological activity of the a-factor. A unified, stereoselective synthetic route to the three geometric isomers of E,E-farnesol (12, 13, and 14) has been developed. The key feature of this synthesis is the ability to control the stereochemistry of triflation of the beta-ketoester 22 to give either 23 or 25. The three farnesol isomers were converted to the corresponding isomeric a-factors (9, 10 and 11) via a modified version of a previously utilized synthetic route. Biological evaluation of these peptides indicates that, surprisingly, all three possess nearly equivalent activity to the natural a-factor bearing the E,E-farnesyl moiety.     

The phototumorigenic fluoroquinolone lomefloxacin photosensitizes pyrimidine dimer formation in human keratinocytes in vitro

The fluoroquinolone antibiotic lomefloxacin is phototoxic, photogenotoxic, photomutagenic and photosensitizes tumorigenesis in mouse skin. We have used T4 endonuclease V to demonstrate that lomefloxacin photosensitizes pyrimidine dimer formation in a human keratinocyte line (HaCaT). A possible mechanism for this effect would be triplet-triplet energy transfer. However, there is indirect evidence that the lomefloxacin triplet yield is very low, making this reaction less likely. The finding that lomefloxacin photosensitizes production of highly mutagenic pyrimidine dimers correlates with its ability to initiate skin tumor formation in mice. Until the potential of other fluoroquinolones to photosensitize dimer formation is explored it may be unadvisable to prescribe these antibiotics to patients with defective DNA repair capacity (e.g. xeroderma pigmentosum).     

The acoustic performance of building façades in hot climates: Part 2—Closed balconies

The acoustic protection afforded by a balcony open to the street but enclosed on all other sides was investigated by means of one-tenth scale models. The results indicate that the protection is slight and the frequency invariant when the receiver is exposed to a direct path. The protection increases with increased sound incident angle and balcony depth and becomes frequency dependent when the direct path between source and receiver is screened.In general, the protection measured by the author, using scale models, compared well with the full-scale measurements of other workers. The measured protection of a balcony is considerably improved when perforated screens of unusual geometry are installed.A maximum protection due to these screens is obtained at first and second floor levels and at balcony depths of 2 m and less.     

Aminocatalytic preparation of bisindolylalkanes

An aminocatalytic method for the formation of bisindolylalkanes is described; the reaction proceeds effectively at ambient temperature in the presence of moisture and air for both aldehyde and ketone substrates and has been applied to the one-step preparation of a series of naturally-occurring bis- and tris-indolylalkanes.     

Evidence for changing of cosmic ray composition between 10(17) and 10(18) eV from multicomponent measurements

The average mass composition of cosmic rays with primary energies between 10(17) and 10(18) eV has been studied using a hybrid detector consisting of the High Resolution Fly's Eye (HiRes) prototype and the MIA muon array. Measurements have been made of the change in the depth of shower maximum and the muon density as a function of energy. The results show that the composition is changing from a heavy to lighter mix as the energy increases.