Chromosomal aberrations in mouse lymphocytes exposed in vitro and in vivo to benzidine and 5 related aromatic amines

Mouse lymphocytes were exposed in vitro for 2 h or in vivo for 24 h to benzidine and related aromatic amines to test for chromosome aberrations (CA) and mitotic indices. Uninduced mouse S9 was used to activate the amines for the in vitro tests to be consistent with the in vivo tests. Contrary to a previous report, no difference could be established in the genotoxicity of benzidine following activation with uninduced S9 compared to induced S9. There were concentration related increases in CA for benzidine and all the amines in vitro except for 4,4'-diaminostilbene which exhibited the greatest cellular toxicity towards cultured lymphocytes. Benzidine and its derivatives showed significant increases in CA in vivo compared to its negative control. The CA values for 4-aminostilbene were significantly higher than the other amines in both in vivo and in vitro studies. These genotoxicity results for 4-aminostilbene are consistent with our previous report of the pronounced CA effects in murine bone-marrow cells but would not be predicted from Salmonella mutagenicity tests.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31873/1/0000823.pd

Substituent effects on the genotoxicity of 4-nitrostilbene derivatives

4-Nitrostilbene and twelve of its derivatives (eleven E-stilbenes and two Z-stilbenes) were examined for possible quantitative structure-activity relationships of their in vitro and in vivo genotoxicity. Relative mutagenicity was studied with and without S9 activation in Salmonella strains TA98 and TA100, as well as in the nitroreductase deficient strains TA98/NR and TA100/NR. Chromosomal aberrations in the bone-marrow cells of mice following intraperitoneal administration of the nitrostilbenes were observed as an indicator of in vivo genotoxicity. All of the compounds were active in TA98 and TA100 without S9 activation, with the exception of 4-amino-4'-nitrostilbene in TA100. Mutagenic activity was greatly reduced or eliminated in the NR strains, which is consistent with metabolic activation of the compounds by bacterial reductase. The presence of S9 lowered the activity of most of the nitrostilbenes presumedly by enzymatic detoxication. Hammet values of substituents, partition coefficients and frontier orbital energies (ELUMO and EHOMO) were studied for correlations with mutagenicity of the eleven E-stilbenes. Correlations could be established between mutagenicity in TA98 without S9 activation and the Hammet values. The same mutagenicity could also be correlated to ELUMO. Rationales for these correlations include the concept that electron-withdrawing groups which lower ELUMO should facilitate the reduction of the nitro group, leading to the proximate mutagen hydroxylamine. The correlations are also explained by the concept that electron-withdrawing groups should help stabilize the hydroxylamine intermediate and make the ultimate mutagenic species, the nitrenium ions, more reactive toward DNA. The relationship between mutagenicity and electronic effects of substituent groups found in vitro could not be extended to the in vivo results. However, except for the dinitrostilbenes, where insolubility prevented their testing, all the nitrostilbenes produced a statistically significant increase in chromosomal aberrations compared to the negative solvent control.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31200/1/0000102.pd

Substituent effects on the in vitro and in vivo genotoxicity of 4-aminobiphenyl and 4-aminostilbene derivatives

4-Amino-4'-substituted biphenyls and 4-aminostilbenes substituted in the 3' or 4' position were studied for their in vitro and in vivo genotoxicity. The in vitro mutagenicity of the biphenyls with and without S9 activation was established with Salmonella strains TA98 and TA100 and that of the stilbenes with the same strains plus TA98/1,8-DNP6. The in vivo genotoxicity assay with both series of compounds was for chromosomal aberrations in the bone-marrow cells of mice following intraperitoneal administration of the chemicals. Hammett values of substituents, partition coefficients and frontier orbital energies (ELUMO and EHOMO) of the compounds were used for correlations with mutagenicity. The Salmonella mutagenicity in TA98 and TA98/1,8-DNP6 with S9 was correlated to Hammett [sigma]+ values for the 4-aminostilbene substituents, showing a strong trend of increasing mutagenicity with an increase in the electron-withdrawing capability of the substituent. Hydrophobicity of the stilbenes, however, had little effect on their relative mutagenicity. The 4-aminobiphenyls showed a correlation between their mutagenicity and Hammett [sigma]+ values of their 4'-substituents in stain TA98 with S9, although the trend was not as strong as for the stilbenes. But unlike the stilbenes, TA98 mutagenicity of the biphenyls could also be correlated to hydrophobicity, and structure-activity correlations for the biphenyls was substantially improved when both [sigma]+ and hydrophobicity data were included. For strain TA100 with S9, little correlation was found between mutagenicity of the stilbenes and any of, the parameters. However, a limited correlation did exist between the mutagenicity of the biphenyls and their hydrophobicity. There was also limited correlations of the mutagenicity for the stilbenes in TA98 and TA98/1,8-DNP6 with S9 to ELUMO or EHOMO. The in vivo genotoxicity results for the biphenyls and stilbenes could not be correlated to electronic effects as for the in vitro results, nor could they be explained by hydrophobicity. However, it is interesting to note that 3'-substituted 4-aminostilbenes were all substantially more genotoxic in vivo than their corresponding 4'-substituted counterparts. The most genotoxic compound in vivo in either series was 4-aminostilbene which would not have been predicted from the in vitro results.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31865/1/0000815.pd

ortho-Substituent effects on the in vitro and in vivo genotoxicity of benzidine derivatives

Benzidine and its 3,3'-diamino, 3,3'-dimethyl, 3,3'-dimethoxy, 3,3'-difluoro, 3,3'-dichloro, 3,3'-dibromo, 3,3'-dicarbomethoxy and 3,3'-dinitro derivatives together with 2-nitrobenzidine and 3-nitrobenzidine were compared for their in vitro and in vivo genotoxicity. Relative mutagenicity was established with Salmonella strains TA98, TA98/1,8-DNP6 and TA100 with and without S9 activation. All the derivatives in the presence of S9 were more mutagenic than benzidine with 3,3'-dinitro- and 3-nitro-benzidine having the greatest mutagenicity. Mutagenicity in all 3 strains with S9 activation could be correlated to electron-withdrawing ability of substituent groups, as measured by the basicity of the amines. This correlation was explained on the basis that electron-withdrawing groups could favor the stability of the mutagenic intermediate N-hydroxylamine and also enhance the reactivity of the ultimate mutagenic species, the nitrenium ion. Mutagenicity was also correlated to the energy of the lowest unoccupied molecular orbitals (ELUMO). Hydrophobicity was found to have very limited effect on the relative mutagenicity of our benzidine derivatives. The in vivo endpoint was chromosomal aberrations in the bone-marrow cells of mice following intraperitoneal administration of benzidine and its derivatives. In contrast to the in vitro results, while all the amines were genotoxic in vivo, only the 3-nitro derivative had a significant increase in toxicity over benzidine.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30582/1/0000219.pd

Measurement of the View the tt production cross-section using eμ events with b-tagged jets in pp collisions at √s = 13 TeV with the ATLAS detector

This paper describes a measurement of the inclusive top quark pair production cross-section (σtt¯) with a data sample of 3.2 fb−1 of proton–proton collisions at a centre-of-mass energy of √s = 13 TeV, collected in 2015 by the ATLAS detector at the LHC. This measurement uses events with an opposite-charge electron–muon pair in the final state. Jets containing b-quarks are tagged using an algorithm based on track impact parameters and reconstructed secondary vertices. The numbers of events with exactly one and exactly two b-tagged jets are counted and used to determine simultaneously σtt¯ and the efficiency to reconstruct and b-tag a jet from a top quark decay, thereby minimising the associated systematic uncertainties. The cross-section is measured to be: σtt¯ = 818 ± 8 (stat) ± 27 (syst) ± 19 (lumi) ± 12 (beam) pb, where the four uncertainties arise from data statistics, experimental and theoretical systematic effects, the integrated luminosity and the LHC beam energy, giving a total relative uncertainty of 4.4%. The result is consistent with theoretical QCD calculations at next-to-next-to-leading order. A fiducial measurement corresponding to the experimental acceptance of the leptons is also presented

Search for TeV-scale gravity signatures in high-mass final states with leptons and jets with the ATLAS detector at sqrt [ s ] = 13TeV

A search for physics beyond the Standard Model, in final states with at least one high transverse momentum charged lepton (electron or muon) and two additional high transverse momentum leptons or jets, is performed using 3.2 fb−1 of proton–proton collision data recorded by the ATLAS detector at the Large Hadron Collider in 2015 at √s = 13 TeV. The upper end of the distribution of the scalar sum of the transverse momenta of leptons and jets is sensitive to the production of high-mass objects. No excess of events beyond Standard Model predictions is observed. Exclusion limits are set for models of microscopic black holes with two to six extra dimensions

The performance of the jet trigger for the ATLAS detector during 2011 data taking

The performance of the jet trigger for the ATLAS detector at the LHC during the 2011 data taking period is described. During 2011 the LHC provided proton–proton collisions with a centre-of-mass energy of 7 TeV and heavy ion collisions with a 2.76 TeV per nucleon–nucleon collision energy. The ATLAS trigger is a three level system designed to reduce the rate of events from the 40 MHz nominal maximum bunch crossing rate to the approximate 400 Hz which can be written to offline storage. The ATLAS jet trigger is the primary means for the online selection of events containing jets. Events are accepted by the trigger if they contain one or more jets above some transverse energy threshold. During 2011 data taking the jet trigger was fully efficient for jets with transverse energy above 25 GeV for triggers seeded randomly at Level 1. For triggers which require a jet to be identified at each of the three trigger levels, full efficiency is reached for offline jets with transverse energy above 60 GeV. Jets reconstructed in the final trigger level and corresponding to offline jets with transverse energy greater than 60 GeV, are reconstructed with a resolution in transverse energy with respect to offline jets, of better than 4 % in the central region and better than 2.5 % in the forward direction

Search for dark matter produced in association with a hadronically decaying vector boson in pp collisions at sqrt (s) = 13 TeV with the ATLAS detector

A search is presented for dark matter produced in association with a hadronically decaying W or Z boson using 3.2 fb−1 of pp collisions at View the MathML sources=13 TeV recorded by the ATLAS detector at the Large Hadron Collider. Events with a hadronic jet compatible with a W or Z boson and with large missing transverse momentum are analysed. The data are consistent with the Standard Model predictions and are interpreted in terms of both an effective field theory and a simplified model containing dark matter

Measurement of the cross section for isolated-photon plus jet production in pp collisions at √s=13 TeV using the ATLAS detector

The dynamics of isolated-photon production in association with a jet in proton–proton collisions at a centre-of-mass energy of 13 TeV are studied with the ATLAS detector at the LHC using a dataset with an integrated luminosity of 3.2 fb−1. Photons are required to have transverse energies above 125 GeV. Jets are identified using the anti- algorithm with radius parameter and required to have transverse momenta above 100 GeV. Measurements of isolated-photon plus jet cross sections are presented as functions of the leading-photon transverse energy, the leading-jet transverse momentum, the azimuthal angular separation between the photon and the jet, the photon–jet invariant mass and the scattering angle in the photon–jet centre-of-mass system. Tree-level plus parton-shower predictions from Sherpa and Pythia as well as next-to-leading-order QCD predictions from Jetphox and Sherpa are compared to the measurements

Search for resonances in the mass distribution of jet pairs with one or two jets identified as b-jets in proton–proton collisions at √s=13TeV with the ATLAS detector

Searches for high-mass resonances in the dijet invariant mass spectrum with one or two jets identi-fied as b-jets are performed using an integrated luminosity of 3.2fb−1of proton–proton collisions with a centre-of-mass energy of √s=13TeVrecorded by the ATLAS detector at the Large Hadron Collider. Noevidence of anomalous phenomena is observed in the data, which are used to exclude, at 95%credibility level, excited b∗quarks with masses from 1.1TeVto 2.1TeVand leptophobic Z bosons with masses from 1.1TeVto 1.5TeV. Contributions of a Gaussian signal shape with effective cross sections ranging from approximately 0.4 to 0.001pb are also excluded in the mass range 1.5–5.0TeV