Paola Rocchi

Processing Capacity Limitations in Pictorial and Spatial Representations in the Totally Congenitally Blind

The study of visuo-spatial imagery abilities in totally congenitally blind people may be instrumental in understanding the contribution of visual experience to imagery processes. In the present paper visuo-spatial imagery capacity was explored through a task devised by Kerr (1987) and adapted for presentation to the blind, in which subjects were asked to imagine either two- or three-dimensional matrices of different complexity and to follow a mental pathway. The first experiment showed that blind people have difficulty with three-dimensional matrices which are within the reach of sighted people, and that their performance is affected by the processing rate. In the second experiment the spatial and pictorial components of visual imagery were analyzed by way of the same spatial task and of a pictorial-tactual task in which subjects had to match a mental representation of a pathway to a tactually explored wire silhouette. On the latter task, blind people did not meet any particular difficulty, probably because they could form representations using other sensory modalities and because they were skillful in tactual exploration. These data suggest that research on the blind cannot easily contribute to the distinction between the spatial and pictorial components of visual imagery.

RXRγ and PPARγ ligands in combination to inhibit proliferation and invasiveness in colon cancer cells

Nuclear retinoid X receptors (RXRs) and peroxisome proliferator-activated receptors (PPARs are potential candidates as drug target for cancer prevention and treatment. We investigated if the rexinoid 6-OH-11-O-hydroxyphenantrene (IIF) potentiates the antitumoral properties of PPARgamma ligands as ciglitazone and pioglitazone, on two colon cancer cell lines: HCA-7 and HCT-116. Drugs inhibited cell growth and induced apoptosis synergistically. The combination resulted in a decrease of cyclooxigenase-2, metalloproteinases-2 and -9 expression level and activity while PPARgamma, RXRgamma and tissue inhibitors of metalloproteinase-1 and -2 expression were increased. Finally, IIF potentiated PPAR transcriptional activity by enhancement of peroxisome proliferator response elements transactivation.

Simple and Dendritic Cyclam Derivatives. Photophysical Properties, Effect of Protonation and Zn2+ Coordination, Preliminary Screening as Inhibitors of Tumour Cell Growth

We have synthesized two novel dendrimers (BG1 and BG2) consisting of a 1,4,8,11-tetraazacyclotetradecane (cyclam, 1) core with appended four dimethoxybenzene and eight benzyl units (BG1) and twelve dimethoxybenzene and sixteen benzyl units (BG2). The absorption and luminescence spectra of these compounds and the changes taking place upon protonation and Zn2+ coordination of their cyclam core have been investigated in acetonitrile-dichloromethane 1:1 v/v solution. For comparison purposes, the absorption and luminescence spectra of 1,4,8,11-tetrabenzyl-cyclam (2), and dendrons BD1 and BD2, model compounds of the branches of BG1 and BG2 respectively, have also been studied. BD1, BD2, BG1, and BG2 exhibit the absorption and emission spectra of their 1,3-dimethoxybenzene unit, but in the two dendrimers the emission intensity is quenched by the cyclam amine groups and increases upon protonation and metal coordination. In order to test if these cyclam derivatives have an antitumour effect, we have studied their action on proliferation in the human neuroblastoma TS12 cell line. Screening experiments have shown that cell proliferation was (i) strongly reduced by the tetrabenzyl substituted cyclam 2, and (ii) unaffected by cyclam and the benzo dendrimers BG1 and BG2. Antitumour screening experiments have also been performed on the tetranaphthyl substituted cyclam 3 and the naphtho-dendrimer NG2, whose photophysical properties have been previously studied. Cell proliferation came out to be moderately reduced by 3, whereas dendrimer NG2 had no effect, similar to dendrimers BG1 and BG2.

Non-enzymatic and microsome-dependent binding of polycyclic hydrocarbons to DNA and polynucleotides

The binding of tritium-labeled 7,12-dimethylbenz[a]anthracene (DMBA), benzo[a]pyrene (BP) and 3-methylcholanthrene (MCA) to DNA or polynucleotides in vitro was re-examined both in the presence and in the absence of rat liver or human placental microsomes. A high level of non-enzymatic binding was evident when thymus DNA was used as acceptor. This non-enzymatic binding made it difficult to determine the effect of microsomes, except in the case of BP when induced rat microsomes were used. Better results were obtained using polynucleotides: a definite microsome-dependent binding occurred between all the polynucleotides and all the hydrocarbons tested. No clear evidence of binding catalysed by microsomes from human placenta was found except in polynucleotide-BP interactions: further studies are required to completely evaluate the ability of such nucleic acid-microsomal system for testing in vitro possible oncogenic substances in animals and humans.

Induction of diphtheria toxin-resistant mutants in human cells by halogenated compounds

SummaryThe mutagenic power of 1,2-dichloroethane, 1,2-dibromoethane, 1,2-diiodoethane was tested in the human cell line, EUE. In our mutagenic system, based on selection against diphtheria toxin, the halogenated compounds, 1,2-dichloroethane and 1,2-dibromoethane revealed a strong mutagenic effect, whereas 1,2-diiodoethane was not mutagenic at a concentration allowing survival of 41%.

Toxic, DNA-damaging and mutagenic activity of epichlorohydrin on human cells cultured in vitro.

Epichlorohydrin (ECHH) highly inhibited the tritiated thymidine uptake by human lymphocytes cultured in vitro, although the corresponding cell viability was unaffected. Furthermore, it elicited unscheduled DNA synthesis, acting as a DNA-damaging agent after its metabolic activation. ECHH also showed a clear toxic and mutagenic activity toward a human epithelial-like cell line, causing a decrease in cell viability and an increase in mutants resistant to 0.05 Lf/ml of diphtheria toxin.

PHOTOINDUCED REACTION OF DIMETHYLNITROSAMINE WITH DNA AND POLYNUCLEOTIDES

Abstract— The interaction between products from dimethylnitrosamine photolytic breakdown and DNA is time‐dependent and the reaction with polyguanylic acid is 36 times higher than that occurring with other polyribonucleotides; such interactions occur only if nucleic acids are present during dimethylnitrosamine photolytic breakdown. Among interaction compounds, neither O6‐methyl‐ nor 7‐methylguanine are observable; on the contrary, N‐methylhydrazine and trimethylamine are always found in acid and alkaline hydrolysates of DNA and polynucleotides. These findings are very similar to the results previously found in biological in vivo and in vitro systems and suggest a possible usefulness of this physicochemical system as an analogical model of chemical carcinogenesis.

The effect of urethan on the synthesis of nucleic acids in the cells of regenerating rat liver.

By administration of urethane (1 mg/g body weight) at the beginning of the S phase i. e. 19 hr after partial hepatectomy the initial rise in DNA synthesis was reversibly inhibited. An inhibitory effect on the total, the soluble, the mitochondral and the microsomal RNA was demonstrated up to 36 hr after hepatectomy. Nach partieller Hepatektomie und Gabe von 1 mg/g Körpergewicht Urethan zum Beginn der S-Phase, d. h. 19 Std nach dem Eingriff, wurde der beginnende Anstieg der DNA-Synthese reversibel gehemmt. Ein Hemmeffekt auf die gesamte, die lösliche, die mitochondriale und die mikrosomale RNA wurde bis 36 Std nach Hepatektomie beobachtet.

Effect of antioxidants on mutagenesis induced by Dmba in human cells

The effect of vitamin A palmitate (VAP), vitamin A acetate (VAA), 2,3-tert-butyl-4-hydroxyanisole, and 2,6-di-tert-butyl-p-cresol (BHT) on mutagenesis induced by 7,12-dime-thylbenz[a]anthracene (DMBA) was examined in a human epithelial-like cell line. Cultures were exposed to DMBA with or without the antioxidant compound, and mutation frequencies were determined by selection against diphtheria toxin. A clear inhibition of mutagenesis was observed particularly with VAA and BHT.

Compared effects of N-hydroxyurethan, urethan and hydroxyurea on DNA synthesis. In vivo and in vitro studies

The effect of N-hydroxyurethan (HUR) on DNA synthesis has been tested both in vivo on various tissues and in vitro on concanavalin A (ConA)-stimulated rat thymocytes and compared with the action of urethan and hydroxyurea. HUR suppresses scheduled DNA synthesis, except that of non-stimulated spleen cells in vitro. The inhibition is efficient and rapid and takes place immediately if the drug is administered at the peak of the S-phase. UR inhibits DNA synthesis in vitro only at much higher doses and with different time course. It is effective or slightly effective if it is administered at the peak of the S-phase. A conversion of urethan into HUR the latter depressing DNA synthesis could partly explain the differences observed. No toxicity was found after treatment with drugs at the concentrations employed. Finally, the relationships between drug doses and cell responses have been particularly observed in vivo.