Methylation of DNA in stomach and small intestine of rats after oral administration of methylamine and nitrite

Young adult male Sprague-Dawley rats were given 30 μmol/kg body weight [l4C]methylamine hydrochloride and 700 μmol/kg body weight sodium nitrite by oral gavage. DNA isolated from the stomach and from the first 15 cm of the small intestine was methylated, containing 7-methylguanine (7mG) at a level of one 7mG molecule per 5×106 and 1×107 nucleotides, respectively. No 7mG was found in the liver at a limit of detection of one 7mG molecule per 2×108 nucleotides. In a second experiment, the excised stomachs were incubated with deoxyribonuclease before the isolation of the DNA in order to degrade DNA in the lumen and in the uppermost lining cells. This treatment resulted in a 30% decrease in the yield of DNA and a 90% reduction in the level of 7mG formation. The results show that nitrosation of a primary alkylamine yields a precursor of an alkylating agent which has a long enough lifetime to diffuse towards and react with intracellular DNA. A correlation of DNA methylation in the stomach with the corresponding tumor formation by the methylating carcinogen N-methyl-N'-nitro-N-nitroso-guanidine was used to estimate the role of DNA damage resulting from endogenous nitrosation of dietary methylamine in man. It was concluded that the risk resulting from this single amine must be negligible but that a similar evaluation of other primary amines is required before the overall role of primary amine nitrosation in the etiology of human gastric cancer can be assesse

Investigation of the covalent binding of styrene-7,8-oxide to DNA in rat and mouse

Styrene-7,8-oxide (SO), the main intermediate metabolite of styrene, induces hyperkeratosis and tumors in the fore-stomach of rats and mice upon chronic administration by gavage. The aim of this study was to investigate whether DNA binding could be responsible for the carcinogenic effect observed. [7-3H]SO was administered by oral gavage in corn oil to male CD rats at two dose levels (1.65 or 240 mg/kg). After 4 or 24 h, forestomach, glandular stomach and liver were excised, DNA was isolated and its radioactivity determined. At the 4 h time point, the DNA radioactivity was below the limit of detection in the forestomach and the liver. Expressed in the units of the covalent binding index, CBI = (μmol adduct/mol DNA nucleotide)/(mmol chemical administered/kg body wt), the DNA-binding potency was below 2.6 and 2.0 respectively. In the glandular stomach at 4 h, and in most 24 h samples, DNA was slightly radiolabeled. Enzymatic degradation of the DNA and separation by HPLC of the normal nucleotides showed that the DNA radioactivity represented biosynthetic incorporation of radiolabel into newly synthesized DNA. The limit of detection of DNA adducts in the glandular stomach was 1.0. In a second experiment, [7-3H]SO was administered by i.p. injection to male B6C3F1 mice. Liver DNA was analyzed after 2 h. No radioactivity was detectable at a limit of detection of CBI < 0.6. In agreement with the relatively long half-life of SO in animals, the chemical reactivity of SO appears to be too low to result in a detectable production of DNA adducts in an in vivo situation. Upon comparison with the DNA-binding of other carcinogens, a purely genotoxic mechanism of tumorigenic action of SO is unlikely. The observed tumorigenic potency in the forestomach could be the result of strong tumor promotion by high-dose cytotoxicity followed by regenerative hyperplasi

Linear dose-response relationship for DNA adducts in rat liver from chronic exposure to aflatoxin B1

Male F-344 rats were given [3H]aflatoxin B1 (AFB 1) in the drinking water at three exposure levels (0.02, 0.6, 20 μg/l, resulting in average dose levels of 2.2, 73, 2110 ng/kg per day). After 4, 6 and 8 weeks, DNA was isolated from the livers and analyzed for aflatoxin- DNA adducts. The level of DNA adducts did not increase significantly after 4 weeks, indicating that a steady-state for adduct formation and removal had nearly been reached. At 8 weeks, the adduct levels were 0.91, 32 and 850 nucleotide-aflatoxin adducts per 109 nucleotides, i.e. clearly proportional ot the dose. At the high dose level, a near 50% tumor incidence would be expected in a 2-year bioassay with F-344 rats while the low dose used is within the range of estimated human dietary exposures to aflatoxin in Western countries. The proportionality seen between exposure and steady-state DNA adduct level is discussed with respect to a linear extrapolation of the turnor risk to low dos

32P-Postlabeling of a DNA adduct derived from 4,4′-methylenedianiline, in the olfactory epithelium of rats exposed by inhalation to 4,4′-methylenediphenyl diisocyanate

Tissues obtained from female Wistar rats exposed to a 0.9 μm aerosol of 4,4′-methylenediphenyl diisocyanate (MDI) for 17 h per day, 5 days per week, for one year, at levels of 0, 0.3, 0.7 and 2.0 mg/m3, were analyzed for DNA adducts. A 32P-postlabeling method was used to detect (i). adducts formed by the reaction of the isocyanate group(s) of MDI with DNA; and a 32P-postlabeling method was adapted to detect (ii), a DNA adduct formed by 4,4′-methylenedianiline (MDA), a hydrolysis/decarboxylation product of MDI. In the lung, neither isocyanate adducts nor the arylamine adduct were detectable. The same negative result was seen in the liver, the bladder, the kidney, the respiratory epithelium and in peripheral lymphocytes. In the olfactory epithelium, on the other hand, the aryl-amine-derived DNA adduct was detected, at the very low levels of 5, 9 and 10 adduct-nucleotides per 1010 nucleotides, for the three dose groups, respectively. The adduct co-chromatographed with the one formed in the liver of rats after oral gavage of MDA. The results are discussed in terms of the importance of genotoxic versus nongenotoxic aspects of carcinogenesi

Dilepton production in heavy ion collisions at intermediate energies

We present a unified description of the vector meson and dilepton production in elementary and in heavy ion reactions. The production of vector mesons ($\rho,\omega$) is described via the excitation of nuclear resonances ($R$). The theoretical framework is an extended vector meson dominance model (eVMD). The treatment of the resonance decays $R\longmapsto NV$ with arbitrary spin is covariant and kinematically complete. The eVMD includes thereby excited vector meson states in the transition form factors. This ensures correct asymptotics and provides a unified description of photonic and mesonic decays. The resonance model is successfully applied to the $\omega$ production in $p+p$ reactions. The same model is applied to the dilepton production in elementary reactions ($p+p, p+d$). Corresponding data are well reproduced. However, when the model is applied to heavy ion reactions in the BEVALAC/SIS energy range the experimental dilepton spectra measured by the DLS Collaboration are significantly underestimated at small invariant masses. As a possible solution of this problem the destruction of quantum interference in a dense medium is discussed. A decoherent emission through vector mesons decays enhances the corresponding dilepton yield in heavy ion reactions. In the vicinity of the $\rho/\omega$-peak the reproduction of the data requires further a substantial collisional broadening of the $\rho$ and in particular of the $\omega$ meson.Comment: 32 pages revtex, 19 figures, to appear in PR

Search for charginos in e+e- interactions at sqrt(s) = 189 GeV

An update of the searches for charginos and gravitinos is presented, based on a data sample corresponding to the 158 pb^{-1} recorded by the DELPHI detector in 1998, at a centre-of-mass energy of 189 GeV. No evidence for a signal was found. The lower mass limits are 4-5 GeV/c^2 higher than those obtained at a centre-of-mass energy of 183 GeV. The (\mu,M_2) MSSM domain excluded by combining the chargino searches with neutralino searches at the Z resonance implies a limit on the mass of the lightest neutralino which, for a heavy sneutrino, is constrained to be above 31.0 GeV/c^2 for tan(beta) \geq 1.Comment: 22 pages, 8 figure

Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS

The chi_b(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb^-1, these states are reconstructed through their radiative decays to Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table, corrected author list, matches final version in Physical Review Letter

Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS

We present the results of a search for new, heavy particles that decay at a significant distance from their production point into a final state containing charged hadrons in association with a high-momentum muon. The search is conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS detector operating at the Large Hadron Collider. Production of such particles is expected in various scenarios of physics beyond the standard model. We observe no signal and place limits on the production cross-section of supersymmetric particles in an R-parity-violating scenario as a function of the neutralino lifetime. Limits are presented for different squark and neutralino masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final version to appear in Physics Letters

Reducing heterotic M-theory to five dimensional supergravity on a manifold with boundary

This paper constructs the reduction of heterotic $M$-theory in eleven dimensions to a supergravity model on a manifold with boundary in five dimensions using a Calabi-Yau three-fold. New results are presented for the boundary terms in the action and for the boundary conditions on the bulk fields. Some general features of dualisation on a manifold with boundary are used to explain the origin of some topological terms in the action. The effect of gaugino condensation on the fermion boundary conditions leads to a `twist' in the chirality of the gravitino which can provide an uplifting mechanism in the vacuum energy to cancel the cosmological constant after moduli stabilisation.Comment: 16 pages, RevTe

Measurement of the inclusive isolated prompt photon cross-section in pp collisions at sqrt(s)= 7 TeV using 35 pb-1 of ATLAS data

A measurement of the differential cross-section for the inclusive production of isolated prompt photons in pp collisions at a center-of-mass energy sqrt(s) = 7 TeV is presented. The measurement covers the pseudorapidity ranges |eta|<1.37 and 1.52<=|eta|<2.37 in the transverse energy range 45<=E_T<400GeV. The results are based on an integrated luminosity of 35 pb-1, collected with the ATLAS detector at the LHC. The yields of the signal photons are measured using a data-driven technique, based on the observed distribution of the hadronic energy in a narrow cone around the photon candidate and the photon selection criteria. The results are compared with next-to-leading order perturbative QCD calculations and found to be in good agreement over four orders of magnitude in cross-section.Comment: 7 pages plus author list (18 pages total), 2 figures, 4 tables, final version published in Physics Letters