6 results on '"K Lutz"'
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2. DNA methylation in the digestive tract of F344 rats during chronic exposure toN-methyl-N-nitrosourea
- Author
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Werner K. Lutz, Hiroko Ohgaki, Irene B. Meier, Paul Kleihues, Barbara I. Ludeke, and Christian Schlatter
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Male ,Cancer Research ,Guanine ,Immunoblotting ,Administration, Oral ,Biology ,Methylation ,Epithelium ,chemistry.chemical_compound ,Esophagus ,Toxikologie ,medicine ,Animals ,ddc:610 ,Pyloric region ,Carcinogen ,Hyperplasia ,Stomach ,Deoxyguanosine ,Methylnitrosourea ,DNA ,General Medicine ,Pylorus ,Molecular biology ,Rats, Inbred F344 ,Rats ,medicine.anatomical_structure ,Bromodeoxyuridine ,Oncology ,Biochemistry ,chemistry ,Purines ,DNA methylation ,Duodenum ,Digestive System ,Cell Division ,DNA Damage - Abstract
The formation of \(O^6\)-methyldeoxyguanosine (\(O^6\)-MedGuo) was determined by an immuno-slot-blot assay in DNA of various tissues of F344 rats exposed to N-methyl-N-nitrosourea (MNU) in the drinking waterat 400 ppm for 2 weeks. Although the pyloric region of the glandular stomach is a target organ under these experimental conditions, the extent of DNA methylation was highest in the forestomach (185 \(\mu\)mol \(O^6\)-MedGuojmol guanine). Fundus (91 J.!moljmol guanine) and pylorus (105 J.!moljmol guanine) of the glandular stomach, oesophagus (124 \(\mu\)mol/mol guanine) and duodenum (109 )lmoljmol guanine) showed lower Ievels of \(O^6\) - MedGuo but differed little between each other. Thus, no correlation was observed between target organ specificity and the extent of DNA methylation. This is in contrast to the gastric carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), which preferentially alkylates DNA of the pylorus, the main site of induction of gastric carcinomas by this chemical. In contrast to MNU, the nonenzymic decomposition of MNNG is accelerated by thiol compounds (reduced glutathione, L-cysteine), which are present at much higher concentrations in the glandular stomach than in the forestomach and oesophagus. During chronic exposure to MNNG (80 ppm), mucosal cells immunoreactive to 0 6-MedGuo are limited to the luminal surface [Kobori et al. (1988) Carcinogenesis 9:2271-2274]. Although MNU (400 ppm) produced similar Ievels of \(O^6\)-MedGuo in the pylorus, no cells containing methylpurines were detectable by immunohistochemistry, suggesting a more uniform methylation of mucosal cells by MNU than by MNNG. After a single oral dose of MNU (90 mg/kg) cells containing methylpurines were unequivocally identified using antibodies to \(O^6\)-MedGuo and the imidazole-ring-opened product of 7-methyldeoxyguanosine. In the gastric fundus, their distribution was similar to those methylated by exposure to MNNG, whereas the pyloric region contained immunoreactive cells also in the deeper mucosallayers. After a 2-week MNU treatment, the rate of cell proliferation, as determined by bromodeoxyuridine immunoreactivity, was only slightly enhanced in the oesophagus andin the fundus, but markedly in the forestomach and the pyloric region of the glandular stomach. lt is concluded that the overall extent of DNA methylation, the distribution of alkylated cells within the mucosa and the proliferative response all contribute to the organ-specific carcinogenicity of MNU.
- Published
- 1991
- Full Text
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3. Stimulation of cell division in the rat by NaCl, KCl, MgCl2, and CaCl2, and inhibition of the sodium chloride effect on the glandular stomach by ascorbic acid and beta-carotene
- Author
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Serena M. Lugli and Werner K. Lutz
- Subjects
Male ,Cancer Research ,medicine.medical_specialty ,Cell division ,Sodium ,Potassium ,Magnesium Chloride ,chemistry.chemical_element ,Stimulation ,Ascorbic Acid ,Calcium ,Sodium Chloride ,Chloride ,Antioxidants ,Potassium Chloride ,S Phase ,Calcium Chloride ,Chlorides ,Internal medicine ,medicine ,Animals ,Chemistry ,Cell growth ,Stomach ,General Medicine ,DNA ,Ascorbic acid ,beta Carotene ,Immunohistochemistry ,Rats, Inbred F344 ,Rats ,Endocrinology ,Oncology ,Bromodeoxyuridine ,Cell Division ,medicine.drug - Abstract
Three questions associated with the stimulation of cell division by chloride salts have been investigated: (i) whether cations other than sodium show a similar effect, (ii) whether vitamins can have a preventive activity, and (iii) whether subchronic treatment with sodium chloride in the diet is also effective. Male Fischer 344 rats were given solutions of the chloride salts of sodium, potassium, magnesium, and calcium by oral gavage. Water was used for control. After 4 h, a 24-h osmotic minipump containing 5-bromo-2'-deoxyuridine was implanted subcutaneously. The forestomach and glandular stomach, as well as liver and bladder were analyzed immunohistochemically 24 h later for the proportion of cells in S phase as an indicator of the rate of replicative DNA synthesis. For both the forestomach and the glandular stomach, potassium was as potent as sodium, and the divalent cations Mg and Ca were even more potent on a molar basis. Supplementation of the diet with ascorbic acid (2 g/kg food) or beta-carotene (12.5 mg/kg food) for 1 week before gavage of the sodium chloride solution resulted in an inhibition of the stimulation of cell division. A putative tumor-chemopreventive activity of the two vitamins might therefore not only rely on their antioxidative properties but may include effects on the cell cycle. A 4-week treatment with a sodium chloride supplement in the diet (2% and 4% supplement) resulted in a significant stimulation of cell division not only in both parts of the stomach and in the bladder (with the 4% supplement) but also in the liver (even with the 2% supplement). Sodium-chloride-stimulated cell turnover therefore is a sustained effect.
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- 1999
4. Absract
- Author
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Marietta Kaszkin, Volker Kinzel, Karl Maly, Irina Bichler, Florian Lang, Hans H. Grunicke, R. Pepperkok, R. Jakobi, P. Lorenz, W. Ansorge, W. Pyerin, P. Borowski, M. Harbers, A. Ludwig, T. Kischel, H. Hilz, K. Eckert, A. Granetzny, J. Fischer, R. Grosse, V. Manch, S. Wehner, B. Kornhuber, U. Ebener, K. Müller-Decker, G. Fürstenberger, I. Vogt, F. Marks, G. Graschew, A. Küsel, W. Hull, W. Lorenz, H. W. Thielmann, Gisela H. Degen, Alexius Freyberger, A. Müller, M. Linscheid, Ulrike Hindermeier, Ute Jorritsma, K. Golka, W. Föllmann, H. Peter, H. M. Bolt, S. Monnerjahn, D. N. Phillips, A. Never, A. Seidel, A. R. Glatt, K. Wiench, E. Frei, P. Schroth, M. Wiessler, T. Schäfer, M. Hergenhahn, E. Hecker, D. Proft, P. Bartholmes, R. S. Bagewadikar, B. Bertram, N. Frank, Hanno Leibersperger, Michael Gschwendt, Friedrich Marks, S. Fasco, Peter Plein, Karin Schiess, Lothar Seidler, T. Jacobi, E. Besemfelder, M. Stephan, W. D. Lehmann, M. Grell, B. Thoma, P. Scheurich, Markus Meyer, Hans Grunicke, G. Jaques, B. Wegmann, K. Ravemann, Odilia Popanda, Heinz Walter Thielmann, H. Voss, U. Wirkner, Dieter Werner, D. Strand, A. Kalmes, H. -P. Walther, B. Mechler, S. Volker Schirrmacher, V. Kinzel, R. Hess, H. -G. Hanagarth, C. Hässler, G. Brandner, Christian Ertel, B. Gückel, V. Schirrmacher, B. A. Kyewski, U. Bogdahn, P. Jachimczak, J. Schneider, W. Brysch, W. Schlingensiepen, D. Drenkard, C. Behl, J. Winkler, R. Apfel, J. Meixensberger, K. Stulle, P. Marquardt, H. P. Vollmers, J. Müller, H. -K. Müller-Hermelink, M. Schuermann, G. Seemann, Angelika Ptok, M. Ptok, T. E. Carey, M. Steffen, U. C. Nitz, B. Everding, F. Hölzel, G. Kantwerk-Funke, G. Boll, K. S. Zänker, P. Hölzel, J. Heymanns, C. Hennig, M. Rotsch, K. Havemann, Jürgen R. Fischer, Sabine Stehr, Harald Lahm, Peter Drings, Peter H. Krammer, M. Kirsch, A. Strubel, A. Kist, R. Hinn, H. Fischer, A. Buttler, G. Schackert, S. Friedenauer, D. Lindner, B. Marczynski, H. Karcls, H. W. Goergens, B. Epe, E. Müller, D. Schütze, S. Boiteux, E. Eder, C. Deininger, C. Hoffman, E. Scherer, E. Vermeulen, H. J. van Kranen, J. Bax, R. A. Woutersen, C. F. van Kreijl, B. Schurich, H. Hagedorn, E. Kamp, G. Eisenbrand, B. Spiegelhalder, U. Bolm-Audorff, H. G. Bienfait, R. Preussmann, C. -D. Wacker, H. Kehl, Z. Akkan, J. Ries, M. Meger, S. E. Shephard, D. Gunz, W. K. Lutz, A. R. Tricker, R. Kurnar, M. Siddiqi, P. Mende, B. Pfundstein, A. Scholl, C. Janzowski, D. Jacob, P. Goelzer, I. Henn, H. Zankl, K. -H. Zimlich, Barbara Gansewendt, Ricarda Thier, K. R. Schroeder, E. Hallier, G. Moeckel, W. Heiden, M. Waldherr-Teschner, J. Brickmann, H. Roeser, G. Krauter, G. Scherer, A. Krätschmer, H. Hauenstein, F. Adlkofer, R. C. Fernando, H. H. Schmeiser, W. Nicklas, Wolfgang Pfau, David H. Phillips, S. Scheckenbach, S. Cantoreggi, Monika Leutbecher, H. Ottenwälder, U. Föst, P. M. Baumgart, H. -C. Kliem, S. Data, C. Pfeiffer, A. Fuchs, P. Schmezer, F. Kuchenmeister, B. L. Pool-Zober, U. M. Liegibel, B. L. Pool-Zobel, L. Steeb, H. Friesel, Th. Schneider, H. R. Scherf, A. Buchmann, R. Bauer-Hofmann, J. Mahr, M. Schwarz, R. Schmidt, F. Rippmann, B. Steinbauer, P. Zlfu, B. Bunk, W. Hefter, K. Klinga, M. R. Berger, L. W. Robertson, G. Luebeck, S. Moolgavkar, U. Torsten, M. Kowalczyk-Wagner, H. Weitzel, Ch. Zechel, H. Peters, F. Anders, S. Ambs, T. Kirchner, H. -G. Neumann, C. Einig, E. Eigenbrodt, D. Oesterle, E. Deml, G. Weisse, U. Gerbracht, H. Stumpf, E. Filsingcr, P. Bannasch, W. Muster, P. Cikryt, P. Münzel, E. Röhrdanz, K. W. Bock, H. -P. Lipp, T. Wiesmüller, H. Hagenmaier, D. Schrenk, A. Karger, G. Bauer, P. Höfler, M. Götschl, E. Viesel, J. Jürgensmeier, D. Schaefer, G. Picht, J. Kiefer, P. Krieg, R. Schnapke, S. Feil, E. Wagner, U. Schleenbecker, A. Anders, M. M. Gross, S. Unger, E. J. Stanbridge, Petra Boukamp, Ulrich Pascheberg, Norbert E. Fusenig, H. Abken, U. H. Weidle, F. Grummt, K. Willecke, R. Schäfer, A. Hajnal, I. Balmer, R. Klemenz, P. E. Goretzki, H. Reishaus, M. Demeure, H. Haubruck, J. Lyons, H. D. Röher, Sylvia Trouliaris, Angelika Hadwiger-Fangmeier, Elke Simon, Heiner Niemann, Teruko Tamura, G. Westphal, Elke Turner, H. Karels, M. Blaszkewicz, Helga Stopper, Dietmar Schiffmann, Umberto De Boni, M. Schuler, R. Schnitzler, M. Metzler, E. Pfeiffer, R. Aulenbacher, T. Langhof, K. R. Schröder, K. Saal, H. K. Müller-Hermelink, W. Henn, G. Seitz, P. Lagoda, A. Christmann, N. Blin, C. Welter, D. Adam, D. Fömzler, C. Winkler, W. Mäueler, M. Schartl, B. Theisinger, G. Schüder, U. Rüther, C. Nunnensiek, H. A. G. Müller, W. Rupp, M. Lüthgens, P. Jipp, I. Kinzler, M. Gulich, H. J. Seidel, O. H. Clark, F. McCormick, H. R. Bourne, F. Gieseler, F. Boege, H. Biersack, B. Spohn, M. Clark, K. Wilms, Fritz Boege, Frank Gieseler, Harald Biersack, Michael Clark, Klaus Wllms, Axel Polack, Lothar Strobl, Regina Feederle, Matthias Schweizer, Dirk Eick, Georg W. Bornkamm, M. Kopun, H. Scherthan, C. Granzow, P. Janiaud, D. Rueß, B. M. Mechler, P. G. Strauss, V. Erfle, M. Fritsche, C. Haessler, H. Christiansen, J. Schestag, N. M. Christiansen, F. Lampert, Wolfgang A. Schulz, Andreas Hasse, Helmut Sies, G. Orend, I. Kuhlmann, W. Doerfler, A. Behn-Krappa, I. Hölker, U. Sandaradura de Silva, Ute Smola, Dagmar Hennig, Angelika Hadviger-Fangmeier, Burkhard Schütz, R. Kerler, H. M. Rabes, G. Dölken, A. A. Fauser, R. Kerkert, U. Ragoczy, R. Fritzen, W. Lange, J. Finke, B. Nowicki, E. Schalipp, W. Siegert, R. Mertelsmann, U. Schilling, H. J. Sinn, W. Maier-Borst, E. A. Friedrich, E. Löhde, M. Lück, H. Raude, H. Schlicker, G. Barzen, E. Kraas, J. Milleck, R. Keymer, S. Störkel, T. Reichert, F. Steinbach, R. Lippold, W. Thoenes, W. Wagner, K. -A. Reiffen, A. Bardosi, D. Brkovic, H. -J. Gabius, B. Brandt, C. Jackisch, D. Seitzer, M. Hillebrand, F. A. Habermann, null Zeindl-Eberhart, null Evelyn, C. Robl, V. Röttgen, C. Nowak, H. -B. Richter-Reichhelm, V. Waldmann, B. Suchy, Ch. Zietz, M. Sarafoff, Richard Ostermayr, Hartmut M. Rabes, J. Lorenz, T. Friedberg, W. Paulus, R. Ferlinz, F. Oesch, E. Jähde, K. -H. Glüsenkamp, L. F. Tietze, M. F. Rajewsky, G. Chen, K. -J. Hutter, J. Bullerdiek, W. J. Zeller, M. Schirner, M. R. Schneider, P. Zbu, M. Gebelein, B. Naser-Hijazi, Nancy E. Hynes, M. Reinhardt, P. Heyl, D. Schmähl, P. Presek, U. Liebenhoff, D. Findik, G. H. Hartmann, C. Kliesch, F. Albert, S. Kunze, M. Wannnenmacher, J. Boese-Landgraf, E. Lorenz, D. Albrecht, M. Dulce, K. R. Aigner, N. Thiem, H. Müller, M. Leonardi, A. Justh, M. Lutz, E. Lang, C. W. v. d. Lieth, H. Sinn, B. R. Betsch, Jan Georg Hengstler, Jürgen Fuchs, Franz Oesch, F. J. Busch, A. B. C. Cato, G. Schied, W. Tang, B. Richter, C. Schaefer, D. K. Kelleher, P. Vaupel, D. Mundt, H. H. Bartsch, H. Meden, M. Meyer, K. Vehmeyer, R. Mull, W. Kuhn, S. Hoffmann, D. Berger, H. Fiebig, Ch. Moog, B. Luu, S. Frühauf, B. K. Keppler, A. Galeano, P. Valenzuela-Paz, T. Klenner, H. Stadler, G. Golomb, E. Breuer, R. Voegeli, P. Hilgard, H. R. Nowrousian, P. Aulenbacher, B. Winterhalter, C. Granson, M. Stöhr, H. Ponstingl, P. Drings, H. Osswald, S. B. Sobottka, E. Amtmann, G. Sauer, B. Hornung, S. Volland, S. Kahl, R. Gerspach, B. Matz, J. Schmidt, M. Lipp, G. Brehm, A. Luz, S. Wendel, P. G. Strauß, V. Erflte, S. Greehmann, A. Zobel, F. Kalkbrenner, G. Vorbrüggen, K. Moelling, T. Iftner, A. H. Müller, P. G. Fuchs, H. Pfister, Klaus Cichutek, Iris Treinies, Matthias Lang, C. Braun, J. Denner, S. Norley, R. Kurth, L. Music, O. D. Wiestler, A. Aguzzi, A. von Deimling, M. Schneemann, R. Elbl, P. Kleihues, H. Land, H. -P. Hohn, M. Höök, H. -W. Denker, W. Kemmner, K. Zaar, Peter A. Jones, R. Kath, M. Herlyn, P. Maier, H. P. Schawalder, J. Elsner, W. Parzefall, E. Erber, R. Sedivy, R. Schulte-Hermann, J. Hemmer, P. Tomakidi, P. Boukamp, D. Breitkreutz, N. E. Fusenig, F. Kallinowski, W. Strauss, A. L. Brownell, I. D. Bassukas, G. Vester, B. Maurer-Schultze, L. Langbein, H. Kosmehl, D. Katenkamp, Eberhard Spiess, Günther Trefz, Werner Ebert, Peter Jordan, Dieter Kübler, Rosemarie B. Lichtner, Marion Wiedemuth, Annette Kittmann, Axel Ullrich, Khashayarsha Khazaie, Aiga Kowitz, Guni Kadmon, Peter Altevogt, U. H. Frixen, J. Behrens, J. Schipper, M. Sachs, H. Birchmeier, R. Hackenberg, Th. Hawighorst, J. Hofmann, H. Beato, K. -D. Schulz, C. Erbil, M. Maasberg, L. A. Kunz, A. Simm, G. Adam, W. Mueller-Klieser, Andreas M. Kaufmann, Michael Stoeck, A. Hülsen, S. Game, M. Donnelly, H. -J. Stark, K. -H. Schlingensiepen, U. Kurzik-Dumke, B. Phannavong, D. Gundacker, E. Gateff, S. Gabius, S. S. Joshi, H. Franz, N. J. John, R. Grümmer, H. W. Denker, M. W. Gross, and U. Karbach
- Subjects
Cancer Research ,Oncology ,General Medicine - Published
- 1991
- Full Text
- View/download PDF
5. Possible implications from results of animal studies in human risk estimations for benzene: nonlinear dose-response relationship due to saturation of metabolism
- Author
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Sandro Grilli, Silvio Parodi, and Werner K. Lutz
- Subjects
Risk ,Cancer Research ,Physiology ,Economic community ,Biology ,medicine.disease_cause ,Toxicology ,Toxikologie ,medicine ,Animals ,Humans ,ddc:610 ,Carcinogen ,Dose-Response Relationship, Drug ,Mutagenicity Tests ,Benzene ,General Medicine ,Metabolism ,Dose–response relationship ,Oncology ,Carcinogens ,Animal studies ,Risk assessment ,Saturation (chemistry) ,Genotoxicity ,Mutagens - Abstract
To date, all risk assessment studies on benzene have been based almost exclusively on epidemiological data. We have attempted a more integrated and quantitative evaluation of carcinogenic risk for humans, trying to utilize, in addition to the epidemiological data, all data available, specifically data on metabolism, genotoxicity, and carcinogenicity in small rodents. An integrated evaluation of the globality of the available data seems to suggest a progressive saturation of metabolic capacity both for man and rodents between 10 and 100 ppm. The most susceptible target cells seem to be different in humans (predominant induction of myelogenous leukemia) and small rodents (induction of a wide variety of tumors). Nevertheless, both epidemiological and experimental carcinogenicity data tend to indicate a flattening of the response for the highest dosages, again suggesting a general saturation of mechanisms of metabolic activation, extended to different target tissues. From a quantitative point of view, the data suggest a carcinogenic potency at 10 ppm two to three times higher than that computable by a linear extrapolation from data in the 100 ppm range. These observations are in accord with the recent proposal of the European Economic Community of reducing benzene time-weighted average occupational levels from 10 to 5 ppm.
- Published
- 1987
- Full Text
- View/download PDF
6. Effect of selected induction of microsomal and nuclear aryl hydrocarbon monooxygenase and epoxide hydrolase as well as cytoplasmic glutathione S-epoxide transferase on the covalent binding of the carcinogen benzo(a)pyrene to rat liver DNA in vivo
- Author
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A. von Däniken, A. Viviani, Ch. Schlatter, and Werner K. Lutz
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Male ,Cancer Research ,Cytoplasm ,Polychlorinated Dibenzodioxins ,In Vitro Techniques ,chemistry.chemical_compound ,Toxikologie ,Animals ,ddc:610 ,Enzyme inducer ,Benzopyrenes ,Epoxide hydrolase ,Carcinogen ,Glutathione Transferase ,Cell Nucleus ,Epoxide Hydrolases ,biology ,General Medicine ,Glutathione ,DNA ,Monooxygenase ,Rats ,Glutathione S-transferase ,Oncology ,Benzo(a)pyrene ,chemistry ,Biochemistry ,Liver ,Enzyme Induction ,Phenobarbital ,biology.protein ,Microsome ,Microsomes, Liver ,Regression Analysis ,Aryl Hydrocarbon Hydroxylases - Abstract
Groups of four adult male rats [ZUR:SIV -Z] were pretreated with corn oil (control; 2 ml/kg/day i. p. for 3 days), trans-stilbene-oxide (SO; 200 mg/kg/day i. p. for 2 days), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 10 \(\mu\)g/kg i. p. once, 4 days before killing), phenobarbital (PB; 1 gjliter in the drinking water for 8 days), and dieldrin (20 mg/kg/day i. p. for 3 or 9 days). They received an injection of [G-\(^3\)H]benzo(a)pyrene (BaP, 31 \(\mu\)g/kg, 7.4. 10\(^9\) dpm/kg; i. v.) 16 h before killing. In the liver of each rat, five enzymatic activities and the covalent binding of BaP to DNA have been determined. The rnicrosomal aryl hydrocarbon monooxygenase activity (AHM) ranged frorn 75% of control (SO) to 356% (TCDD), the nuclear AHM from 63% (SO) to 333% (TCDD). Microsomal epoxide hydrolase activity (EH) was induced up to 238% (PB), nuclear EH ranged from 86% (TCDD) to 218% (PB). A different extent of induction was observed in the two compartments. Highest induction of glutathione S-epoxide transferase activity (GST) was found with PB (202%). The DNA binding of BaP was modulated within 79% (dieldrin, 9 days) and 238% of control (TCDD). An enzyme digest of control DNA was analysed by Sephadex LH-20 chromatography. Multiple linear regression analysis with all data expressedas o/o of control yielded the following equation: DNA Binding = 1.49 · Microsomal AHM- 1.07 · Nuclear AHM+ 0.33 · Microsomal EH- 0.52 · N uclear EH+ 0.11 · Cytoplasmic GST + 58.2. From this analysis it is concluded that (1) AHM located in the endoplasmic reticulum is most important in the formation of DNA-binding metabolites, (2) EH in the same compar.tment is not determinative in thls respect nor has it a protective effect, (3) both membrane-bound enzyme activities located in the nucleus may inactivate potential ultimate carcinogens, and ( 4) cytoplasmic GST probably cannot reduce DNA binding due to its subcellular localization.
- Published
- 1980
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