TY  - JOUR
A1  - Singh, Jasbir
A1  - Dani, Harinder M.
A1  - Sharma, Reeta
A1  - Steinberg, Pablo
T1  - Inhibition of the biosynthesis of SRP polypeptides and secretory proteins by aflatoxin B-1 can disrupt protein targeting
JF  - Cell biochemistry and function
N2  - Cell culture and western blotting studies revealed that aflatoxin B-1 (AFB(1)) inhibits the biosynthesis of two of the constituent polypeptides of signal recognition particle (SRP) (SRP54 and 72). SRP escorts polyribosomes carrying signal peptides from free form in the cytosol to the bound form on endoplasmic reticulum (ER) membrane during protein targeting. These effects of AFB(1) on SRP biosynthesis may inhibit the formation of functional SRP Our experiments have further shown that AFB(1) also inhibits the biosynthesis/translocation of a secretory protein, preprolactin, which fails to appear in the lumen of ER consequent to the treatment with this hepatocarcinogen. The results of the experiments presented in this article therefore enable us to infer for the first time that aflatoxin B-1 may inhibit the functioning of SRP as an escort and deplete the ER of polyribosomes for secretory protein synthesis. As these secretory proteins are important components of the plasma membrane, gap junctions and intercellular matrix, their absence from these locations could disturb cell to cell communication leading to tumorigenesis.
KW  - aflatoxin B-1
KW  - SRP
KW  - protein targeting
KW  - protein translocation
KW  - western blotting
Y1  - 2005
U6  - https://doi.org/10.1027/cbf.1285
SN  - 0263-6484
VL  - 24
SP  - 507
EP  - 510
PB  - Wiley
CY  - Chichester
ER  - 
TY  - JOUR
A1  - Singh, Jasbir
A1  - Singh, S.
A1  - Dani, H. M.
A1  - Sharma, Reeta
A1  - Steinberg, Pablo
T1  - Interactions of aflatoxin B-1 with SRP components can disrupt protein targeting
N2  - Spectrofluorimetric studies have revealed that aflatoxin B-1 (AFB(1)) interacts with signal recognition particle (SRP), which acts as an escort for polyribosomes with signal peptides to be transported and bound to the cytoplasmic face of the endoplasmic reticulum (ER). We further report that the binding of AFB(1) to SRP is selective as it only binds to two (SRP9 and 14) out of its three constituent polypeptides studied. Binding of AFB(1) to proteins is known to alter their conformations. Interactions of AFB(1) with SRP polypeptides may generate structural and functional alterations in this particle and hinder secretory protein synthesis. Copyright (C) 2004 John Wiley Sons, Ltd
Y1  - 2005
SN  - 0263-6484
ER  - 
TY  - JOUR
A1  - Fuchs, J.
A1  - Teubner, Wera
A1  - Steinberg, Pablo
T1  - The resistance of intestinal epithelial cells towards the transforming activity of 2-hydroxyamino-1-methyl-6- phenylimidazo[4,5-B]pyridine is accompanied by glutathione S-transferase induction
Y1  - 2004
SN  - 0028-1298
ER  - 
TY  - JOUR
A1  - Teubner, Wera
A1  - Langheinrich, C.
A1  - Seidel, Albrecht
A1  - Steinberg, Pablo
T1  - Inhibition of p53 transactivation activity does not promote mutagen-induced transformation of IEC-18
Y1  - 2004
SN  - 0028-1298
ER  - 
TY  - JOUR
A1  - Stark, Avishay abraham
A1  - Porat, Noga
A1  - Volohonsky, Gloria
A1  - Konlosh, A.
A1  - Bluvshtein, Evgenia
A1  - Tubi, C.
A1  - Steinberg, Pablo
T1  - The role of gamma-glutamyl transpeptidase in the biosynthesis of glutathione
Y1  - 2003
ER  - 
TY  - JOUR
A1  - Okano, J.
A1  - Shiota, G.
A1  - Matsumoto, K.
A1  - Yasui, S.
A1  - Kurimasa, A.
A1  - Hisatome, I.
A1  - Steinberg, Pablo
A1  - Murawaki, Y.
T1  - Hepatocyte growth factor exerts a proliferative effect on oval cells through the PI3K/AKT signaling pathway
Y1  - 2003
ER  - 
TY  - JOUR
A1  - Bartsch, Ingrid
A1  - Zschaler, Ingrid
A1  - Haseloff, Monika
A1  - Steinberg, Pablo
T1  - Establishment of a long-term culture system for rat colon epithelial cells
N2  - The aim of this study was to establish a long-term culture. system for rat colon epithelia isolaled by incubating a 4-cm-long rat colon segment cut longitudinally with all ethylenediaminetetraacetic acid [disodium salt]- containing buffer, taken up in conditioned medium from the normal rat kidney fibroblast cell line NRK (i.e., the supernatant Of pure NRK cultures), directly plated on mitomycin C-treated NRK cells and subcultured with conditioned medium from NRK cells. Cells started to migrate out of the crypts shortly after plating them on NRK feeder layers. Some of the crypts fell apart during the isolation procedure. whereas the vast majority of them did it within I to 2 Ill after plating. The cells proliferated extremely slowly but continuously over a period of 4 mo and were epithelial because they expressed cytokeratin 19 and were stained by crystal violet at pH 2.8. In conclusion, the experimental system described ill this study allows to maintain rat colon epithelial cells for up to 4 mo in culture and can be used to Study the effects of a variety of tumor-modulating factors on growth and gene expression of normal colon epithelial cells in vitro
Y1  - 2003
UR  - http://www.springerlink.com/content/120498/
U6  - https://doi.org/10.1290/0404035.1
SN  - 1071-2690
ER  - 
TY  - JOUR
A1  - Barlow, S. M.
A1  - Greig, J. B.
A1  - Bridges, J. W.
A1  - Carere, A.
A1  - Carpy, A. J.
A1  - Galli, Corrado L.
A1  - Kleiner, J.
A1  - Knudsen, I.
A1  - Koeter, H. B.
A1  - Levy, L. S.
A1  - Madsen, C.
A1  - Mayer, S.
A1  - Narbonne, J. F.
A1  - Pfannkuch, F.
A1  - Prodanchuk, M. G.
A1  - Smith, Mason R.
A1  - Steinberg, Pablo
T1  - Hazard identification by methods of animal-based toxicology
Y1  - 2002
ER  - 
TY  - JOUR
A1  - Dybing, E.
A1  - Doe, J.
A1  - Groten, J.
A1  - Kleiner, J.
A1  - O'Brien, J.
A1  - Renwick, A. G.
A1  - Schlatter, J.
A1  - Steinberg, Pablo
A1  - Tritschler, A.
A1  - Walker, R.
A1  - Younes, M.
T1  - Hazard characterisation of chemicals in food and diet : dose response, mechanisms and extrapolation issues
Y1  - 2002
ER  - 
TY  - JOUR
A1  - Volohonsky, Gloria
A1  - Tuby, Chen N. Y. H.
A1  - Porat, Noga
A1  - Wellman-Rousseau, Maria
A1  - Visvikis, Athanase
A1  - Leroy, Pierre
A1  - Rashi, Sharon
A1  - Steinberg, Pablo
A1  - Stark, Avishay Abraham
T1  - A spectrophotometric assay of gamma-glutamylcysteine synthetase and glutathione synthetase in crude extracts from tissues and cultured mammalian cells
Y1  - 2002
ER  - 
TY  - GEN
A1  - Steinberg, Pablo
T1  - Only one Component of a holistic Nutrition Policy
T1  - Nur ein Baustein einer ganzheitlichen Ernährungspolitik
T2  - Fleischwirtschaft
Y1  - 2018
SN  - 0015-363X
VL  - 98
IS  - 11
SP  - 8
EP  - 9
PB  - Deutscher Fachverlag GmbH
CY  - Frankfurt am Main
ER  - 
TY  - GEN
A1  - Scholtka, Bettina
A1  - Schneider, Mandy
A1  - Melcher, Ralph
A1  - Katzenberger, Tiemo
A1  - Friedrich, Daniela
A1  - Berghof-Jäger, Kornelia
A1  - Scheppach, Wolfgang
A1  - Steinberg, Pablo
T1  - A gene marker panel covering the Wnt and the Ras-Raf-MEK-MAPK signalling pathways allows to detect gene mutations in 80% of early (UICC I) colon cancer stages in humans
N2  - Background: Very recently a gene marker panel that allows the mutational analysis of APC, CTNNB1, B-RAF and K-RAS was conceived. The aim of the present study was to use the 4-gene marker panel covering the Wnt and Ras-Raf-MEK-MAPK signalling pathways to determine the percentage of sporadic colorectal carcinomas (CRC) carrying at least one of the four above-mentioned genes in a mutated form alone and/or in combination with microsatellite instability (MSI) and to compare the sensitivity of the gene marker panel used in this study with that of gene marker panels previously reported in the scientific literature. Methods: CTNNB1 and B-RAF were screened by PCR-single-strand conformation polymorphism analysis and K-RAS gene mutations by restriction fragment length polymorphism analysis. For the mutational analysis of the APC gene mutation cluster region (codons 1243–1567) direct DNA sequencing was performed. The U.S. National Cancer Institute microsatellite panel (BAT25, BAT26, D2S123, D5S346 and D17S250) was used for MSI analysis. Results: It could be shown that about 80% of early stage CRC (UICC stages I and II) and over 90% of CRC in the UICC stage IV carried at least one mutated gene and/or showed MSI. No significant increase in the gene mutation frequencies could be determined when comparing tumours in the UICC stage I with those in UICC stage IV. Conclusions: When compared with previously published gene marker panels the 4-gene marker panel used in the present study shows an excellent performance, allowing to detect genetic alterations in 80–90% of human sporadic CRC samples analyzed.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - paper 120 
KW  - Colorectal carcinomas
KW  - K-RAS
KW  - Microsatellite instability
KW  - Oncogenes
KW  - Tumour suppressor genes
Y1  - 2009
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus-44587
ER  - 
TY  - JOUR
A1  - Kühnel, Dana
A1  - Steinberg, Pablo
A1  - Scholtka, Bettina
T1  - A human-relevant dose of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PHIP) can induce precancerous lesions in rat intestine after 6 months of exposure
Y1  - 2004
SN  - 0028-1298
ER  - 
TY  - JOUR
A1  - Hacker, Hans-Jörg
A1  - Steinberg, Pablo
A1  - Bannasch, Peter
T1  - Pyruvate kinase isoenzyme shift from L-type to M2-type is a late event in hepatocarcinogenesis induced in rats by a choline-deficient/DL-ethionine supplemented diet
Y1  - 1998
ER  - 
TY  - JOUR
A1  - Mueller, Carsten
A1  - Ullmann, Kristina
A1  - Wilkens, Andrea
A1  - Winterhalter, Peter
A1  - Toyokuni, Shinya
A1  - Steinberg, Pablo
T1  - Potent antioxidative activity of vineatrol (R) 30 grapevine-shoot extract
N2  - The health promoting effects of a grapevine-shoot extract named Vineatrol (R) 30, which contains resveratrol (Resv) as well as considerable amounts of Resv oligomers, have recently been investigated. In the present study, we analyzed the free radical scavenging capacity, the ability to inhibit lipid peroxidation, and the capacity to enhance the human glutathione peroxidase 1 (GPx) and the human superoxide dismutase 1 (SOD) gene promoter activities of Vineatrol (R) 30. Vineatrol (R) 30 was able to scavenge the 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid radical cation and led to concentration-dependent inhibition of lipid peroxidation, Vineatrol (R) 30 not being superior to Resv alone in both cases. Vineatrol (R) 30 also enhanced the gene promoter activities of human GPx and SOD expressed in V79 cells, whereas this effect could not be demonstrated for Resv. In summary, the results presented in this study show that the Vineatrol (R) 30 grapevine-shoot extract is a free radical scavenger and potent antioxidant at non- eytotoxic concentrations.
Y1  - 2009
UR  - http://www.jstage.jst.go.jp/browse/bbb
U6  - https://doi.org/10.1271/Bbb.90213
SN  - 0916-8451
ER  - 
TY  - JOUR
A1  - Müller, Carsten
A1  - Ullmann, Kristina
A1  - Steinberg, Pablo
T1  - The grapevine-shoot extract Vineatrol30 Inhibits the chemically induced malignant transformation of BALB/c-3T3 Cells
JF  - Journal of medicinal food
N2  - Vineatrol (R) 30 (developed and produced jointly by Breko GmbH [Bremen, Germany] and Actichem [Montauban, France]) is a grapevine-shoot extract that contains resveratrol as well as considerable amounts of resveratrol oligomers. In the present study it is shown that Vineatrol30 at a noncytotoxic concentration of 2.3 mu g/mL significantly reduced the number of malignantly transformed foci induced by a sequential treatment of BALB/c-3T3 cells with 3-methylcholanthrene and 12-O-tetradecanoylphorbol 13-acetate in the so-called BALB/c-3T3 cell transformation assay. At a higher concentration Vineatrol30 drastically decreased the relative plating efficiency of the cells. Furthermore, the results suggest that the resveratrol oligomers present in Vineatrol30, independently from resveratrol itself, were indeed able to inhibit the formation of malignantly transformed BALB/c-3T3 foci.
KW  - BALB/c-3T3 cells
KW  - cell transformation assay
KW  - resveratrol
KW  - resveratrol oligomers
KW  - Vineatrol (R) 30
Y1  - 2011
U6  - https://doi.org/10.1089/jmf.2010.0022
SN  - 1096-620X
VL  - 14
IS  - 1-2
SP  - 34
EP  - 39
PB  - Liebert
CY  - New Rochelle
ER  - 
TY  - JOUR
A1  - Steinberg, Pablo
A1  - Zschaler, Ingrid
A1  - Thom, Elke
A1  - Kuna, Manuela
A1  - Wüst, Günter
A1  - Schäfer-Schwebel, Angelika
A1  - Müller, Rolf
A1  - Kramer, Peter-Jürgen
A1  - Weiße, Günter
T1  - The polycyclic musk 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthaline lacks liver tumor initiating and promoting activity in rats exposed to human-relevant doses
Y1  - 2001
UR  - http://www.springerlink.com/content/100462
U6  - https://doi.org/10.1007/s002040100274
SN  - 0340-5761
ER  - 
TY  - JOUR
A1  - Komlosh, A.
A1  - Volohonsky, Gloria
A1  - Porat, Noga
A1  - Tuby, chen n. y. h.
A1  - Bluvshtein, Evgenia
A1  - Steinberg, Pablo
A1  - Oesch, Franz
A1  - Stark, Avishay Abraham
T1  - Gamma-glutamyl transpeptidase and glutathione biosynthesis in non-tumorigenic and tumorigenic rat liver oval cell lines
Y1  - 2001
ER  - 
TY  - JOUR
A1  - Hengstler, Jan Georg
A1  - Utesch, D.
A1  - Steinberg, Pablo
T1  - Cryopreserved primary hepatocytes as a constantly available in vitro model for the evaluation of human and animal drug metabolism and enzyme induction
Y1  - 2000
ER  - 
TY  - JOUR
A1  - Schleger, C.
A1  - Heck, R.
A1  - Steinberg, Pablo
T1  - The role of wild-type and mutated N-ras in the malignant transformation of liver cells
Y1  - 2000
ER  - 
TY  - JOUR
A1  - Hengstler, Jan Georg
A1  - Ringel, M.
A1  - Biefang, Katja
A1  - Hammel, S.
A1  - Milbert, U.
A1  - Gerl, M.
A1  - Klebach, M.
A1  - Diener, B.
A1  - Platt, Karl-Ludwig
A1  - Böttger, Thomas
A1  - Steinberg, Pablo
A1  - Oesch, Franz
T1  - Cultures with cryopreserved hepatocytes : applicability for studies of enzyme induction
Y1  - 2000
ER  - 
TY  - JOUR
A1  - Steinberg, Pablo
A1  - Klingelhöffer, Alexandra
A1  - Schäfer, Angelika
A1  - Wüst, Günter
A1  - Weiße, Günter
A1  - Oesch, Franz
A1  - Eigenbrodt, Erich
T1  - Expression of pyruvate kinase M2 in preneoplastic hepatic foci of N-nitrosomorpholine-treated rats
Y1  - 1999
ER  - 
TY  - JOUR
A1  - Mazurek, Sybille
A1  - Eigenbrodt, Erich
A1  - Failing, Klaus
A1  - Steinberg, Pablo
T1  - Alterations in the glycolytic and glutaminolytic pathways after malignant transformation of rat liver oval cells
Y1  - 1999
ER  - 
TY  - JOUR
A1  - Steinberg, Pablo
A1  - Fischer, Thomas M.
A1  - Arand, Michael
A1  - Park, Eunju
A1  - Elmadfa, Ibrahim
A1  - Rimkus, Gerhard
A1  - Brunn, Hubertus
A1  - Dienes, Hans-Peter
T1  - Acute hepatotoxicity of the polycyclic musk 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthaline (AHTN)
Y1  - 1999
ER  - 
TY  - JOUR
A1  - Bluvshtein, Evgenia
A1  - Glass, George
A1  - Volohonsky, Gloria
A1  - Yaakubowitz, Margalit
A1  - Harness, Ella
A1  - Smorodinsky, Nechama
A1  - Seidel, Albrecht
A1  - Frank, Heinz
A1  - Stark, Avishay Abraham
A1  - Steinberg, Pablo
T1  - Inhibition of the hydrolytic and transpeptidatic activities of rat kidney gamma-glutamyltranspeptidase by specific monoclonal antibodies
Y1  - 1999
ER  - 
TY  - JOUR
A1  - Schleger, C.
A1  - Becker, Rolf
A1  - Oesch, Franz
A1  - Steinberg, Pablo
T1  - The human p53 gene mutated at position 249 per se is not sufficient to immortalize human liver cells
Y1  - 1999
ER  - 
TY  - JOUR
A1  - Hengstler, Jan Georg
A1  - VanDerBurg, Bart
A1  - Steinberg, Pablo
A1  - Oesch, Franz
T1  - Interspecies differences in cancer susceptibility and toxicity
Y1  - 1999
ER  - 
TY  - JOUR
A1  - Steinberg, Pablo
A1  - Fischer, Thomas M.
A1  - Kiulies, Sandra
A1  - Biefang, Katja
A1  - Platt, Karl-Ludwig
A1  - Oesch, Franz
A1  - Böttger, Thomas
A1  - Bulitta, Clemens
A1  - Kempf, Peter
A1  - Hengstler, Jan Georg
T1  - Drug metabolizing capacity of cryopreserved human, rat and mouse liver parenchymal cells in suspension
Y1  - 1999
ER  - 
TY  - JOUR
A1  - Schulz, Tim Julius
A1  - Thierbach, Renè
A1  - Voigt, Anja
A1  - Drewes, Gunnar
A1  - Mietzner, Brun
A1  - Steinberg, Pablo
A1  - Pfeiffer, Andreas F. H.
A1  - Ristow, Michael
T1  - Induction of oxidative metabolism by mitochondrial frataxin inhibits cancer growth : Otto Warburg revisited
N2  - More than 80 years ago Otto Warburg suggested that cancer might be caused by a decrease in mitochondrial energy metabolism paralleled by an increase in glycolytic flux. In later years, it was shown that cancer cells exhibit multiple alterations in mitochondrial content, structure, function, and activity. We have stably overexpressed the Friedreich ataxia-associated protein frataxin in several colon cancer cell lines. These cells have increased oxidative metabolism, as shown by concurrent increases in aconitase activity, mitochondrial membrane potential, cellular respiration, and ATP content. Consistent with Warburg's hypothesis, we found that frataxin-overexpressing cells also have decreased growth rates and increased population doubling times, show inhibited colony formation capacity in soft agar assays, and exhibit a reduced capacity for tumor formation when injected into nude mice. Furthermore, overexpression of frataxin leads to an increased phosphorylation of the tumor suppressor p38 mitogen-activated protein kinase, as well as decreased phosphorylation of extracellular signal-regulated kinase. Taken together, these results support the view that an increase in oxidative metabolism induced by mitochondrial frataxin may inhibit cancer growth in mammals
Y1  - 2006
UR  - http://www.jbc.org/content/281/2/977.full.pdf+html
U6  - https://doi.org/10.1074/jbc.M511064200
ER  - 
TY  - JOUR
A1  - Thierbach, René
A1  - Drewes, Gunnar
A1  - Fusser, Markus
A1  - Voigt, Anja
A1  - Kuhlow, Doreen
A1  - Blume, Urte
A1  - Schulz, Tim Julius
A1  - Reiche, Carina
A1  - Glatt, Hansruedi
A1  - Epe, Bernd
A1  - Steinberg, Pablo
A1  - Ristow, Michael
T1  - The Friedreich's ataxia protein frataxin modulates DNA base excision repair in prokaryotes and mammals
N2  - DNA-repair mechanisms enable cells to maintain their genetic information by protecting it from mutations that may cause malignant growth. Recent evidence suggests that specific DNA-repair enzymes contain ISCs (iron-sulfur clusters). The nuclear-encoded protein frataxin is essential for the mitochondrial biosynthesis of ISCs. Frataxin deficiency causes a neurodegenerative disorder named Friedreich's ataxia in humans. Various types of cancer occurring at young age are associated with this disease, and hence with frataxin deficiency. Mice carrying a hepatocyte- specific disruption of the frataxin gene develop multiple liver tumours for unresolved reasons. In the present study, we show that frataxin deficiency in murine liver is associated with increased basal levels of oxidative DNA base damage. Accordingly, eukaryotic V79 fibroblasts overexpressing human frataxin show decreased basal levels of these modifications, while prokaryotic Salmonella enterica serotype Typhimurium TA 104 strains transformed with human frataxin show decreased mutation rates. The repair rates of oxidative DNA base modifications in V79 cells overexpressing frataxin were significantly higher than in control cells. Lastly, cleavage activity related to the ISC-independent repair enzyme 8-oxoguanine glycosylase was found to be unaltered by frataxin overexpression. These findings indicate that frataxin modulates DNA-repair mechanisms probably due to its impact on ISC-dependent repair proteins, linking mitochondrial dysfunction to DNA repair and tumour initiation.
Y1  - 2010
UR  - http://www.biochemj.org/bj/toc.htm
U6  - https://doi.org/10.1042/Bj20101116
SN  - 0264-6021
ER  - 
TY  - JOUR
A1  - Thierbach, René
A1  - Blume, Urte
A1  - Wolfrum, K.
A1  - Drewes, Gunnar
A1  - Voigt, Anja
A1  - Ristow, Michael
A1  - Steinberg, Pablo
T1  - Altered carbohydrate metabolism in a tumour developing knock-out mice model
Y1  - 2010
UR  - http://www.springerlink.com/content/100530
U6  - https://doi.org/10.1007/s00210-010-0508-7
SN  - 0028-1298
ER  - 
TY  - JOUR
A1  - Thierbach, René
A1  - Drewes, Gunnar
A1  - Fusser, Markus
A1  - Wolfrum, Kathrin
A1  - Epe, Bernd
A1  - Ristow, Michael
A1  - Steinberg, Pablo
T1  - A role for iron-sulfur cluster proteins in DNA repair
Y1  - 2009
UR  - http://www.springerlink.com/content/100530
U6  - https://doi.org/10.1007/s00210-009-0404-1
SN  - 0028-1298
ER  - 
TY  - JOUR
A1  - Thierbach, Renè
A1  - Schulz, Tim Julius
A1  - Isken, Frank
A1  - Voigt, Aanja
A1  - Mietzner, Brun
A1  - Drewes, Gunnar
A1  - von Kleist-Retzow, Jürgen-Christoph
A1  - Wiesner, Rudolf J.
A1  - Magnuson, Mark A.
A1  - Puccio, Helene
A1  - Pfeiffer, Andreas F. H.
A1  - Steinberg, Pablo
A1  - Ristow, Michael
T1  - Targeted disruption of hepatic frataxin expression causes impaired mitochondrial function, decreased life span and tumor growth in mice
N2  - We have disrupted expression of the mitochondrial Friedreich ataxia protein frataxin specifically in murine hepatocytes to generate mice with impaired mitochondrial function and decreased oxidative phosphorylation. These animals have a reduced life span and develop multiple hepatic tumors. Livers also show increased oxidative stress, impaired respiration and reduced ATP levels paralleled by reduced activity of iron-sulfur cluster (Fe/S) containing proteins (ISP), which all leads to increased hepatocyte turnover by promoting both apoptosis and proliferation. Accordingly, phosphorylation of the stress-inducible p38 MAP kinase was found to be specifically impaired following disruption of frataxin. Taken together, these findings indicate that frataxin may act as a mitochondrial tumor suppressor protein in mammals
Y1  - 2005
ER  - 
TY  - JOUR
A1  - Thierbach, Rene
A1  - Schulz, Tim Julius
A1  - Voigt, Aanja
A1  - Drewes, Gunnar
A1  - Isken, F.
A1  - Pfeiffer, Andreas F. H.
A1  - Ristow, Michael
A1  - Steinberg, Pablo
T1  - Targeted disruption of frataxin in hepatocytes causes spontaneous neoplasia accompanied by increased ROS formation
Y1  - 2004
SN  - 0028-1298
ER  - 
TY  - JOUR
A1  - Thierbach, Rene
A1  - Florian, Simone
A1  - Wolfrum, Katharina
A1  - Voigt, Anja
A1  - Drewes, Gunnar
A1  - Blume, Urte
A1  - Bannasch, Peter
A1  - Ristow, Michael
A1  - Steinberg, Pablo
T1  - Specific alterations of carbohydrate metabolism are associated with hepatocarcinogenesis in mitochondrially impaired mice
JF  - Human molecular genetics
N2  - Friedreich's ataxia is an inherited neurodegenerative disease caused by the reduced expression of the mitochondrially active protein frataxin. We have previously shown that mice with a hepatocyte-specific frataxin knockout (AlbFxn(-/-)) develop multiple hepatic tumors in later life. In the present study, hepatic carbohydrate metabolism in AlbFxn(-/-) mice at an early and late life stage was analyzed. In young (5-week-old) AlbFxn(-/-) mice hepatic ATP, glucose-6-phosphate and glycogen levels were found to be reduced by similar to 74, 80 and 88%, respectively, when compared with control animals. This pronounced ATP, G6P and glycogen depletion in the livers of young mice reverted in older animals: while half of the mice die before 30 weeks of age, the other half reaches 17 months of age and exhibits glycogen, G6P and ATP levels similar to those in age-matched controls. A key event in this respect seems to be the up-regulation of GLUT1, the predominant glucose transporter in fetal liver parenchyma, which became evident in AlbFxn(-/-) mice being 5-12 weeks of age. The most significant histological findings in animals being 17 or 22 months of age were the appearance of multiple clear cell, mixed cell and basophilic foci throughout the liver parenchyma as well as the development of hepatocellular adenomas and carcinomas. The hepatocarcinogenic process in AlbFxn 2/2 mice shows remarkable differences regarding carbohydrate metabolism alterations when compared with all other chemically and virally driven liver cancer models described up to now.
Y1  - 2012
U6  - https://doi.org/10.1093/hmg/ddr499
SN  - 0964-6906
VL  - 21
IS  - 3
SP  - 656
EP  - 663
PB  - Oxford Univ. Press
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Herbst, Uta
A1  - Fuchs, Iris Judith
A1  - Teubner, Wera
A1  - Seidel, Albrecht
A1  - Frank, Heinz
A1  - Steinberg, Pablo
T1  - Malignant transformation of human colon epithelial cells by polycyclic aromatic hydrocarbons and heterocyclic aromatic amines
Y1  - 2004
SN  - 0028-1298
ER  - 
TY  - JOUR
A1  - Herbst, Uta
A1  - Fuchs, Iris Judith
A1  - Teubner, Wera
A1  - Steinberg, Pablo
T1  - Malignant transformation of human colon epithelial cells by benzo[c]phenanthrene dihydrodiolepoxides as well as 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine
N2  - Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic amines (HCAs) ingested with food have repeatedly been suggested to be involved in the malignant transformation of colon epithelial cells. In order to test this hypothesis, HCEC cells (SV40 large T antigen-immortalized human colon epithelial cells) were incubated with a racemic mixture of benzo[c]phenanthrene dihydrodiol epoxides (B[c]PhDE), extremely potent carcinogenic PAH metabolites in vivo, or with 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhIP), the N-hydroxylated metabolite of the most abundant HCA in cooked meat. First, it was shown that HCEC cells express sulfotransferase 1A1, which is needed to metabolize N-OH-PhIP to the corresponding N-sulfonyloxy derivative, the direct precursor molecule of genotoxic nitrenium ions. Thereafter, exponentially growing HCEC cells were exposed five times to 0.1 mu g (0.37 nmol) B[c]PhDE/ml for 30 min or 0.72 mu g (3 mnol) N-OH-PhTP/ml for 24 h. Chemically treated HCEC cells showed an enhanced saturation density and grew faster than the corresponding solvent-treated cell cultures. After five treatment cycles, HCECB[c]PhDE as well as HCECN-OH-PhIP cells lost cell-cell contact inhibition and started piling up and forming foci in the culture flasks. Furthermore, HCECB[c]phDE and HCECN-OH-PhIP cells were injected i.m. into SCID mice. Within 6 weeks after injection, eight animals out of eight injected with HCECB[c]phDE or HCECN-OH-PhIP cells developed tumors at the site of injection, thus demonstrating the high tumorigenic potential of the HCECB[c]PhDE and HCECN-OH-PhIP cell cultures. Taken together, we show for the first time that the abovementioned active PAH metabolites as well as N-OH-PhIP are indeed able to malignantly transform human colon epithelial cells in vitro.
Y1  - 2006
UR  - http://www.sciencedirect.com/science/journal/0041008X
U6  - https://doi.org/10.1016/j.taap.2005.07.016
SN  - 0041-008X
ER  - 
TY  - GEN
A1  - Scholtka, Bettina
A1  - Kühnel, Dana
A1  - Taugner, Felicitas
A1  - Steinberg, Pablo
T1  - Inflammation does not precede or accompany the induction of perneoplastic lesions in the colon of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-fed rats
N2  - Heterocyclic aromatic amines (HCAs) are formed in meat cooked at high temperatures for a long time or over an open flame. In this context 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), the most abundant HCA in cooked meat, has been suggested to be involved in colon and prostate carcinogenesis. In the latter case it has been reported that: (1) roughly 50% of Fischer F344 male rats treated with PhIP develop carcinomas in the ventral prostate lobe at 1 year of age; (2) inflammation precedes prostatic intraepithelial neoplasia in PhIP-fed rats; (3) inflammation specifically occurs in the ventral prostate lobe of PhIP-fed rats. To test whether PhIP by itself leads to inflammation in the colon and whether a human-relevant concentration of PhIP is able to induce preneoplastic lesions in the colon, male F344 rats were fed 0.1 or 100 ppm PhIP for up to 10 months and thereafter the colon tissue was analyzed histochemically. In none of the experimental groups signs of acute or chronic colonic inflammation were observed. 0.1 ppm PhIP leads to the development of hyperplastic and dysplastic lesions in the colon of single animals, but the incidence of these lesions does not reach a statistical significance. In contrast, in rats fed 100 ppm PhIP for 10 months hyperplastic and dysplastic colonic lesions were induced in a statistically significant number of animals. It is concluded that: (1) the induction of preneoplastic lesions in rat colon by PhIP is not preceded or accompanied by an inflammatory process; (2) a human-relevant concentration of PhIP alone is not sufficient to initiate colon carcinogenesis in rats.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - paper 119 
KW  - Colorectal cancer
KW  - Heterocyclic aromatic amines
KW  - Inflammation
Y1  - 2009
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus-44570
ER  -