@article{NolteLorenzenLehretal.1992, author = {Nolte, D. and Lorenzen, A. and Lehr, H.-A. and Zimmer, F.-J. and Klotz, Karl-Norbert and Messmer, K.}, title = {Reduction of postischemic leukocyte-endothelium interaction by adenosine via A\(_2\) receptor}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-60424}, year = {1992}, abstract = {The adhesion of leukocytes to the endothelium of postcapillary venules hallmarks a key event in ischemia-reperfusion injury. Adenosine has been shown to protect from postischemic reperfusion injury, presumably through inhibition of postischemic leukocyte-endothelial interaction. This study was performed to investigate in vivo by which receptors the effect of adenosine on postischemic leukocyte-endothelium interaction is mediated. The hamster dorsal skinfold model and fluorescence microscopy were used for intravital investigation of red cell velocity, vessel diameter, and leukocyte-endothelium interaction in postcapillary venules of a thin striated skin muscle. leukocytes were stained in vivo with acridine orange (0.5 mg kg\(^{-1}\) min\(^{-1}\) i.v. ). Parameters were assessed prior to induction of 4 h ischemia to the muscle tissue and 0.5 h, 2 h, and 24 h after reperfusion. ·Adenosine, the adenosine A1-selective agonist 2-chloro-N\(^6\) -cyclopentyladenosine (CCPA), the Arselective agonist CGS 21,680, the non-selective adenosine receptor antagonist xanthine amine congener {XAC), and the adenosine uptake blocker S-(p-nitrobenzyl)-6-thioinosine (NBTI) were infused viajugular vein starting 15 min priortorelease of ischemia until 0.5 h after reperfusion. Adenosine and CGS 21,680 significantly reduced postischemic leukocyte-endothelium interaction 0.5 h after reperfusion (p< 0.01), while no inhibitory effect was observed with CCPA. Coadministration of XAC blocked the inhibitory effects of adenosine. Infusion of NBTI alone effectively decreased postischemic leukocyte-endothelium interaction. These findings indicate that adenosine reduces postischemic leukocyte-endothelium interaction via A\(_2\) receptor and suggest a protective role of endogenous adenosine during ischemia-reperfusion.}, subject = {Toxikologie}, language = {en} } @article{MeierBratschiLutzSchlatter1983, author = {Meier-Bratschi, A. and Lutz, Werner K. and Schlatter, C.}, title = {Methylation of liver DNA of rat and mouse by N-nitrosodimethylamine formed in vivo from dimethylamine and nitrite}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61052}, year = {1983}, abstract = {The extent of formation of N-nitrosodimethylaminc {NDMA) in the stomachs of rats and mice after sirnultancous oral administration of [\(^{14}\)C]dimethylamine and potassium nitrite was determined by measuring the methylation of liver DNA. With doses of around 1 mg dimethylamine hydrochloride/ kg body weight and 50 mg potassium nitrite/kg body weight. 0,8 \% of the amine was nitrosated on average. The individual fluctuations ranged from 0.2 to 1.30\% in the rat and from 0.2 to 1.9\% in the mouse. Simultaneous administration of 50 mg sodium ascorbate (vitamin Cl/kg body weight inhibited the nitrosation by ahout 80\% while 50 mg \(\alpha\)-tocopherol acetate [Vitamin E)/kg body weight reduced the nitrosation by about a half. Assuming similar kinctics and conditions of nitrosation in rats and man. a comparison of the formation of NDMA in vivo from dietary dimethylamine and nitrite with the estimated human uptake of preformed N DMA revealed that in vitro formation in the stomach of man is probably negligible.}, subject = {Toxikologie}, language = {en} } @article{MeierShephardLutz1990, author = {Meier, I. and Shephard, S. E. and Lutz, Werner K.}, title = {Nitrosation of aspartic acid, aspartame, and glycine ethylester. Alkylation of 4-(p-nitrobenzyl)pyridine (NBP) in vitro and binding to DNA in the rat}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-60804}, year = {1990}, abstract = {In a colorimetric assay using 4-( p-nitrobenzyl)pyridine (NBP) as a nucleophilic scavenger of alkylating agents, the nitrosation and alkylation reactions were investigated for a number of amino acids and derivatives. The alkylating activity increased with the square of the nitrite concentration. The nitrosation rate constants for aspartic acid, aspartame, and glycine ethylester ( = precursors C) were 0.08, 1.4 and ~ 0.2, respectively, expressed in terms of the pH-dependent \(k_2\) rate constant of the equation dNOCjdt = \(k_2\) • (C]· [nitrite]\(^2\) • The rates correlated inversely with the basicity of the amino group. The stability of the alkylating activity was astonishingly high, both in acid and at neutral pH. Half-lives of 500, 200, and 30 min were determined for aspartic acid (pH 3.5), aspartame (pH 2.5), and glycine ethylester (pH 2.5). Values of 60, 15, and 2 min; respectively, were found at pH 7. It is concluded that rearrangement of the primary N-nitroso product to the ultimate alkylating agent could be rate-limiting. The potential of nitrosated a-amino acids to bind to DN A in vivo was investigated by oral gavage of radiolabelled glycine ethylester to rats, followed irnmediately by sodium nitrite. DNA was isolated from stomach and liver and analysed for radioactivity and modified nucleotides. No indication of DNA adduct formation was obtained. Based on an estimation of the dose fraction converted from glycine ethylester to the nitroso product under the given experimental conditions, the maximum possible DNA-binding potency of nitroso glycine ethylester is about one order of magnitude below the methylating potency of N-nitrosomethylurea in rat stomach. The apparent discrepancy to the in vitro data could be due to efficient detoxification processes in mammalian cells.}, subject = {Toxikologie}, language = {en} } @article{MarinovichLutz1985, author = {Marinovich, M. and Lutz, Werner K.}, title = {Covalent binding of aflatoxin B\(_1\) to liver DNA in rats pretreated with ethanol}, series = {Experientia}, volume = {41}, journal = {Experientia}, number = {10}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-55237}, pages = {1338 -- 1340}, year = {1985}, abstract = {Male Fischer F-344 rats were given ethanol in the drinking water and/or by single oral administration. Following this, the animals received p.o. 100 ng/kg of the hepatocarcinogen eHJaflatoxin BI (AFBI)' 24 h later, the level of DNA-bound AFBI was determined in the liver and was found not to be affected by any type of ethanol pretreatment. A cocarcinogenic effect of ethanol in the liver is therefore unlikely to be due to an effect on the metabolic activation and inactivation processes governing the formation of DNA-binding AFBI metabolites.}, subject = {Toxikologie}, language = {en} } @article{LutzWinklerDunitz1971, author = {Lutz, Werner K. and Winkler, F. K. and Dunitz, J. D.}, title = {Crystal structure of the antibiotic monensin similarities and differences betweeen free acid and metal complex}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61228}, year = {1971}, abstract = {The structure of monensin, C36H620 11 , has been deterrnined by X-ray analysis of its crystalline monohydrate (orthorhombic, a = 15.15, b = 23.61, c = 10.65 A, Z = 4, space group P212121). Phases were assigned by direct methods, malring use of the 'tangent formula'. Although the conformation of the free acid resembles that of the silver salt in being cyclic, there are differences in the hydrogen bonding pattern. These featurcs are discussed in relation to the cornplexation of metal ions by m.onensin.}, subject = {Toxikologie}, language = {en} } @article{LutzViviantSchlatter1978, author = {Lutz, Werner K. and Viviant, A. and Schlatter, C.}, title = {Nonlinear dose-response relationship for the binding of the carcinogen benzo(a)pyrene to rat liver DNA in vivo}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61179}, year = {1978}, abstract = {Wlth radioactive compound of high specific activity, the binding of carcinogene to DNA can be measured wlth doses that are ineffective ln long-term studies. The binding of tritiated benzo(a )pyrene to liver DNA of adult male rats has been determined 50 hr after a singie l.p. injection of doses between 40 1'9/kg and 4 mg/kg. The doseresponse relationship is linear up to 1 mg/kg, shows a step towards 2 mg/kg, and gives a shallow linear slope above that value. The observed binding ranges from 1.7 to 180 nmoles benzo(a)pyrene per mole DNA phosphate. The nonlinearity could be due to an induction of metabolizing enzymes. The microsomal aryl hydrocarbon hydroxylase activity increases significantly 24 hr after a single dose of 4 mg/kg and 48 hr after doses of 2 and 4 mg/kg, but no induction Ia found with 1 mg/kg. The binding from an equimolar dose is 35 times lower than the one found on mouse skin DNA and 300 times lower than that of N,Ndlmethylnitrosamine in rat liver. A good correlatlon exiats to the respective tumor formation in long-term studles.}, subject = {Toxikologie}, language = {en} } @article{LutzSchlatter1992, author = {Lutz, Werner K. and Schlatter, J.}, title = {Chemical carcinogens and overnutrition in diet-related cancer [commentary]}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-60712}, year = {1992}, abstract = {The intake of known dietary carclnogens was compiled and the cancer risk was estlmated on the basis of carcinogenic potencies in animals as derived from the Carcinogenic Potency Database by Gold and co-workers. The total cancer risk was compared with the number of cancer cases attributed by epidemiologists to dietary factors (one-third of all cancer cases, i.e. -80 000 per one million Jives). Except for alcohol, the known dietary carcinogens could not account for more than a few bundred cancer cases. Tbis was seen both with tbe DNA-reactive carcinogens (beterocyclic aromatic amines, polycyclic aromatic hydrocarbons, N-nitroso compounds, estragole, aflatoxin B., ethyl carbamate, to name the most important factors) as wen as with those carclnogens wbich have not been shown to react with DNA (e.g. caffelc acid and the carcinogeruc metals arsenic and cadmium). Residues and contaminants turned out to be negligible. Among the various pmsibilities to explain the discrepancy we investigated the roJe of ovemutritlon. Dietary restriction in animals is weil known for its strong reducing effect on spontaneous tumor formation. These data can be used to derive a carcinogenic potency for excess macronutrients: tbe tumor incidence seen with the restrlcted animals is taken as a control value and the increased tumor incidence in the animals fed ad libitum is attributed to the additional feed iotake. For excess standard diet in rats, a carcinogenic potency TD50 of 16 glkg/day was deduced from a recent study. Ovemutrition in Switzerland, estimated to be 5.5 kcallkg/day, was converted to excess food (1.9 g/kg/day) and tbe cancer incidence was calculated. The result, 60 000 cancer cases per one million Jives, is provocatively close to the number of cases not explained by the known dietary chemical carcinogens. Mechanistic studies will be required to test our hypothesis and investigate the role of different types of macronutrients in ovemutrition.}, subject = {Toxikologie}, language = {en} } @article{LutzSchlatter1977, author = {Lutz, Werner K. and Schlatter, C.}, title = {Saccharin does not bind to DNA of liver or bladder in the rat [Short Communication]}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61194}, year = {1977}, abstract = {No abstract available}, subject = {Toxikologie}, language = {en} } @article{LutzSchlatter1977, author = {Lutz, Werner K. and Schlatter, C.}, title = {Mechanism of the carcinogenic action of benzene: irreversible binding to rat liver DNA}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61208}, year = {1977}, abstract = {No abstract available}, subject = {Toxikologie}, language = {en} } @article{LutzSchlatter1978, author = {Lutz, Werner K. and Schlatter, C.}, title = {A closed inhalation system for pharmacokinetic and metabolism studies of volatile compounds with small laboratory animals}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-80145}, year = {1978}, abstract = {In the inhalation system described an animal can be kept in the same atmosphere of a 2-liter desiccator for up to 24 h. The expired carbon dioxide is adsorbed with soda lime and the resulting reduced pressure is balanced by a supply of oxygen also used for the inflow of the chemical to be investigated. Urine and faeces can be collected ~eparately and the system allows a periodical control of the concentration of the chemical by sampling the air with needle and syringe.}, subject = {Toxikologie}, language = {en} }