Alessandra Forni

Are chromosome aberrations in circulating lymphocytes predictive of future cancer onset in humans? Preliminary results of an Italian cohort study

To investigate the existence of an association between the frequency of chromosome aberrations (CA) in non-target tissues and cancer risk, a historical cohort study was carried out in a group of 1455 subjects screened for CA over the last 20 years in Italy. Statistically significant increases in standardized mortality ratio (SMR) for all cancers were found in subjects with medium and high levels of CA in peripheral blood lymphocytes (SMR = 178.5 and SMR = 182.0, respectively) and in subjects with high levels of CA for respiratory tract cancers (SMR = 250.8) and lymphatic and hematopoietic tissue neoplasms (SMR = 548.8). Significant trends in the SMRs were observed for these latter causes of death.

Chromosome Studies in Workers Exposed to Benzene or Toluene or Both

Chromosome studies were carried out on peripheral blood lymphocytes of 34 workers of a rotogravure plant, and in 34 controls matched for sex and age. Ten of the workers were exposed to benzene before 1953 and then to toluene, and 24 have been exposed only to toluene after 1953. The proportions of unstable and stable chromosome aberrations were significantly higher statistically in the benzene group compared with the controls, and in the benzene group in comparison with the toluene group. No significant differences were found between the frequencies of chromosome changes in the toluene and control groups.

Chromosome Changes and Their Evolution in Subjects With Past Exposure to Benzene

Chromosome studies of peripheral blood lymphocytes in 25 subjects who had recovered from benzene hemopathy, in four subjects with bone marrow toxicity from benzene, and in three subjects who had recovered from acute benzene poisoning revealed significantly increased rates of “unstable” and “stable” chromosome aberrations which, In most cases, were still present several years after cessation of exposure to the toxic agent and recovery from the poisoning. The follow-up cytogenetic studies showed a tendency toward a decrease in unstable chromosome changes and, generally, a persistence or an increase in stable changes. Bn some cases there was evidence of abnormal clone formation in peripheral blood lymphocytes. Chromosomes of the G group seemed to be involved in stable changes with a frequency higher than expected.

Cancer predictive value of cytogenetic markers used in occupational health surveillance programs: a report from an ongoing study by the European Study Group on Cytogenetic Biomarkers and Health

The cytogenetic endpoints in peripheral blood lymphocytes: chromosomal aberrations (CA), sister chromatid exchange (SCE) and micronuclei (MN) are established biomarkers of exposure for mutagens or carcinogens in the work environment. However, it is not clear whether these biomarkers also may serve as biomarkers for genotoxic effects which will result in an enhanced cancer risk. In order to assess this problem, Nordic and Italian cohorts were established, and preliminary results from these two studies indicated a predictive value of CA frequency for cancer risk, whereas no such associations were observed for SCE or MN. A collaborative study between the Nordic and Italian research groups, will enable a more thorough evaluation of the cancer predictivity of the cytogenetic endpoints. We here report on the establishment of a joint data base comprising 5271 subjects, examined 1965-1988 for at least one cytogenetic biomarker. Totally, 3540 subjects had been examined for CA, 2702 for SCE and 1496 for MN. These cohorts have been followed-up with respect to subsequent cancer mortality or cancer incidence, and the expected values have been calculated from rates derived from the general populations in each country. Stratified cohort analyses will be performed with respect to the levels of the cytogenetic biomarkers. The importance of potential effect modifiers such as gender, age at test, and time since test, will be evaluated using Poisson regression models. The remaining two potential effect modifiers, occupational exposures and smoking, will be assessed in a case-referent study within the study base.

Initial occupational exposure to lead. Chromosome and biochemical findings.

Serial chromosome and biochemical studies were carried out in 11 subjects before and during initial occupational exposure to moderate quantities of lead fumes in a storage battery plant. The rate of abnormal metaphases, mostly with chromatid and one-break chromosome aberrations, was approximately doubled after one month of work; it further increased after two months of work; remained in this range up to seven months of exposure; and then tended to decrease somewhat. Blood lead levels increased progressively in the first few months, then reached a steady state. Urinary lead and coproporphyrin levels increased sharply after one month of work, while urinary delta-aminolevulinic acid (ALA) levels increased moderately. The ALA dehydratase (ALAD) activity of red blood cells (RBCs) was reduced to almost 50% of the initial values after one month, decreased further in subsequent months, and remained decreased through the remainder of the study.

Halogen Bonds with Benzene : an Assessment of DFT Functionals

The performance of an extensive set of density functional theory functionals has been tested against CCSD(T) and MP2 results, extrapolated to the complete basis set (CBS) limit, for the interaction of either DCl or DBr (D = H, HCC, F, and NC) with the aromatic system of benzene. It was found that double hybrid functionals explicitly including dispersion, that is, B2PLYPD and mPW2PLYPD, provide the better agreement with the CCSD(T)/CBS results on both energies and equilibrium geometry, indicating the importance of dispersive contributions in determining this interaction. Among the less expensive functionals, the better performance is provided by the ωB97X and M062X functionals, while the ωB97XD and B97D functionals are shown to work very well for bromine complexes but not so well for chlorine complexes.

A central site for the hyperglycemic action of 2-deoxy-D-glucose in mouse and rat

Abstract The hyperglycemic effect of 2-deoxy-D-glucose (2-DG), a specific inhibitor of intracellular glucose utilization, given into the lateral brain ventricle has been evaluated and compared to that evoked by the systemic administration of the drug. 2-DG given centrally in the mouse or the rat was active at 1 16 or 1 6 respectively of the dose which was effective by intraperitoneal route, suggesting the existence of a central site for the action of this drug. In mice lesioned in the hypothalamus by goldthioglucose, the hyperglycemic effect of intraventricularly administered 2-DG was considerably reduced. In the light of these results the possible site of the glucosensitive elements of the brain is briefly discussed.

Supramolecular hierarchy among halogen and hydrogen bond donors in light-induced surface patterning†

Halogen bonding, a noncovalent interaction possessing several unique features compared to the more familiar hydrogen bonding, is emerging as a powerful tool in functional materials design. Herein, we unambiguously show that one of these characteristic features, namely high directionality, renders halogen bonding the interaction of choice when developing azobenzene-containing supramolecular polymers for light-induced surface patterning. The study is conducted by using an extensive library of azobenzene molecules that differ only in terms of the bond-donor unit. We introduce a new tetrafluorophenol-containing azobenzene photoswitch capable of forming strong hydrogen bonds, and show that an iodoethynyl-containing azobenzene comes out on top of the supramolecular hierarchy to provide unprecedented photoinduced surface patterning efficiency. Specifically, the iodoethynyl motif seems highly promising in future development of polymeric optical and photoactive materials driven by halogen bonding.

Cooperation between Cis and Trans Influences in cis-PtII(PPh3)2 Complexes: Structural, Spectroscopic, and Computational Studies

The relevance of cis and trans influences of some anionic ligands X and Y in cis-[PtX(2)(PPh(3))(2)] and cis-[PtXY(PPh(3))(2)] complexes have been studied by the X-ray crystal structures of several derivatives (X(2) = (AcO)(2) (3), (NO(3))(2) (5), Br(2) (7), I(2) (11); and XY = Cl(AcO) (2), Cl(NO(3)) (4), and Cl(NO(2)) (13)), density functional theory (DFT) calculations, and one bond Pt-P coupling constants, (1)J(PtP). The latter have allowed an evaluation of the relative magnitude of both influences. It is concluded that such influences act in a cooperative way and that the cis influence is not irrelevant when rationalizing the (1)J(PtP) values, as well as the experimental Pt-P bond distances. On the contrary, in the optimized geometries, evaluated through B3LYP/def2-SVP calculations, the cis influence was not observed, except for compounds ClPh (21), Ph(2) (22), and, to a lesser extent, Cl(NO(2)) (13) and (NO(2))(2) (14). A natural bond order analysis on the optimized structures, however, has shown how the cis influence can be related to the s-character of the Pt hybrid orbital involved in the Pt-P bonds and the net atomic charge on Pt. We have also found that in the X-ray structures of cis-[PtX(2)(PPh(3))(2)] complexes the two Pt-X and the two Pt-P bond lengths are different each other and are related to the conformation of the phosphine groups, rather than to the crystal packing, since this feature is observed also in the optimized geometries.

Polymorphism-dependent aggregation induced emission of a push-pull dye and its multi-stimuli responsive behavior†

A comprehensive optical investigation of 1,1-dicyano-2,2-bis(4-dimethylaminophenyl)ethylene (1) is presented. The compound crystallizes in four different forms all displaying AIE behavior. The crystalline forms A and B are yellow-orange-emissive, while C and D are green-emissive. On the basis of X-ray structural analysis, the weak intermolecular interactions account for restricted internal rotations, leading to fluorescence enhancement in the crystals; however, the difference in emission color is ascribed to the various conformations of the molecules in the four crystalline forms. In addition, the emission color of crystals of A can be tuned by heating and grinding, that of B by grinding only, while crystals of C show chronochromic behavior. An explanation for such a rich variety of luminescence behavior is formulated here through the use of steady state and time resolved photoluminescence, X-ray diffraction analysis and DFT and TDDFT calculations. The involved chromic mechanism appears to be mainly associated with surface defects induced by the external stimuli rather than an amorphization process, as frequently observed for other stimuli responsive compounds.